Showing posts with label personalized medicine. Show all posts
Showing posts with label personalized medicine. Show all posts

July 02, 2008

Dr Daniel Haber's cancer circulating tumor cell blood test CTC chip used to track cancer progress in realtime

The blood test requires a 10 milliliter blood sample -- just two teaspoons. It takes about eight hours to send the blood across the 80,000 tiny columns so a specially designed antibody glue can latch onto passing cancer cells. It was used to detect cancer in 27 people and helped to track the progress of cancer in near real time. This will help determine what treatments are working and a genetic fingerprint of the current state of any tumor. This should lead to better cancer treatment and earlier detection and better disease monitoring

Haber and his colleagues analyzed blood samples from 27 patients with non-small cell lung cancer, 23 who had EGFR gene mutations and four who did not. CTCs were identified in all samples and in genetic analyses from mutations 92 percent of the time.

Mutations in EGFR, a protein, can help predict whether these tumors will respond to a family of drugs called tyrosine kinase inhibitors.

"Even in the three to four months that we followed patients, the genetic make-up of the tumors changed. Resistant mutations appear and other mutations appear, obviously because we're doing things [with drug therapy] to the cancer," Haber said. "But the way we practice oncology we don't typically test for that. We do one biopsy which takes a tiny, tiny amount and assume that for the rest of the course, the tumor is the same."

"It's important to know in real time what you're treating," he continued. "We need to be able to follow the patient without needing to re-biopsy the tumor every time."




A previous study published in Nature used the CTC (Circulating Tumor Cells) chip technology to look at CTCs in lung, pancreatic, prostate, breast and colon cancers. The CTC chip successfully found such cells in 99 percent of the samples.

Schiller, of the University of Texas Southwestern Medical Center in Dallas, said there are practical questions about whether enough cells can be extracted to make the technique effective and whether it will work for other types of tumors.

Haber said he believes it will.

The CTC chip, licensed to the privately held CellPoint Diagnostics in Mountain View, California, is 100 times more sensitive than a U.S. Food and Drug Administration-approved technique that uses magnetic beads to try to extract cancer cells, according to Haber.

"I think this is key to personalized medicine," said Dr. Daniel Haber, senior author of a paper detailing the technology, to be published in the July 24 issue of the New England Journal of Medicine but released early online Wednesday. "As we get to targeted therapies in increasing numbers, and increasing understanding about the genetics that guide targeted therapies, we need a way to know what we're treating."

The technology is in its infancy, however. "This is still in a very, very early stage where it takes a long time to handle every sample, to flow the blood through the chip," Haber said. "This is a proof of principle that we can do this. We need a much more automated system for larger clinical trials."

Dr. Len Horovitz, a pulmonary specialist at Lenox Hill Hospital in New York City, said that "you have to have some circulating cells to do this test, but it's very exciting because they're getting a genetic fingerprint of a tumor which will tell an oncologist what therapy the tumor might respond to or not respond to.

"It's expensive, but it may well be that if we can identify patients who can have a personalized regimen that works, we will be saving the cost of treating all those patients with regimens that don't work," he added.


FURTHER
Megpagetoday coverage

Web MD coverage of the CTC chip

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June 30, 2008

Zinc Finger Proteins Put Personalized HIV Therapy Within Reach

- Researchers at the University of Pennsylvania School of Medicine and collaborators are using minute, naturally occurring proteins called zinc fingers to engineer T cells to one day treat AIDS in humans.

The first steps have been taken towards the goal of using modified T cells from an HIV-infected person for their own treatment. They showed that, using the zinc fingers, they could reduce the viral load of immune-deficient mice transplanted with engineered T cells.

Normally, zinc fingers bind to different bases in the DNA sequence to regulate the activity of genes. The zinc fingers used in this experiment were designed to bind to specific DNA sequences in the CCR5 gene. The CCR5 protein is one of the two cell-surface receptors needed for HIV to gain entry into a T cell in order to replicate.

In this study, the zinc finger protein brings a DNA enzyme to the CCR5 gene to cut a portion of its sequence, but due to the repair process a new mutation arises in the CCR5 protein, rendering it non-functional. Without a functional CCR5 protein on the cell's surface, HIV cannot enter, presumably leading to resistance to HIV infection.



The researchers demonstrated this process in cell culture and in a mouse model. For the animal part of the study, the investigators used healthy human CD4 T cells and added DNA that expresses the zinc fingers, which modifies the CCR5 co-receptor. They grew the engineered cells in tissue culture flasks and transferred them into immune-deficient mice infected with HIV. "We followed them over time and showed that those mice that received the zinc-finger-treated cells showed less viral load than controls and improved CD4 counts," says Perez.

The researchers are planning a clinical trial in humans in which T cells from HIV patients would have their CCR5 gene deliberately knocked out. These modified T cells could then be infused back into the patients to re-establish their immune system and decrease their viral load.

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Participated in a podcast on the Speculist about the Future of Fit and Fat

Sunday night Phil Bowermaster and Stephen Gordon hosted a panel on The Future of of Fit (and Fat). The panelists were PJ Manney, Brian Wang, and fitness expert and entrepreneur Shawn Phillips.

Shawn Phillips is an author, entrepreneur, and expert in the area of performance training and nutrition. He created the Full Strength® Premium Nutrition Shake, clinically proven to swap body fat for lean muscle. He is the author of ABSolution: The Practical Guide to Building Your Best Abs and has just released Strength for Life, published by Ballantine/Random House.

PJ Manney is a writer and futurist and a leading voice in the H+ movement. She has written extensively on transhumanism and related topics, as well as for television (Xena Warrior Princess and Hercules the Legendary Journeys) , and has a novel under development. PJ is the Chairman of the board of directors of the World Transhumanist Association, she's a senior associate at the Foresight Nanotech Institute, and she is on the scientific advisory board for the Lifeboat Foundation.

Brian L. Wang, M.B.A. is the Director of Research for the Lifeboat Foundation. Brian is a long time futurist who has been involved with nanotechnology associations since 1994. He is now a member of the Center for Responsible Nanotechnology (CRN) Task Force where he moderates the technology sub-task force. He is also on the Nanoethics Group Advisory Board. He is also the mastermind behind Next Big Future.


Check out the notes on the podcast and the podcast itself over at the Speculist.

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Electrostatic-based DNA Microarray Technique Could Revolutionize Medical Diagnostics


A team of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) has invented a technique in which DNA or RNA assays — the key to genetic profiling and disease detection — can be read and evaluated without the need of elaborate chemical labeling or sophisticated instrumentation.

Based on electrostatic repulsion — in which objects with the same electrical charge repel one another — the technique is relatively simple and inexpensive to implement, and can be carried out in a matter of minutes.

"One of the most amazing things about our electrostatic detection method is that it requires nothing more than the naked eye to read out results that currently require chemical labeling and confocal laser scanners," said Jay Groves, a chemist with joint appointments at Berkeley Lab's Physical Biosciences Division and the Chemistry Department of the University of California (UC) at Berkeley, who led this research. "We believe this technique could revolutionize the use of DNA microarrays for both research and diagnostics."

Groves, who is also a Howard Hughes Medical Institute (HHMI) investigator, and members of his research group Nathan Clack and Khalid Salaita, have published a paper on their technique in the journal Nature Biotechnology, which is now available online. The paper is entitled "Electrostatic readout of DNA microarrays with charged microspheres."

In their paper, Groves, Clack, and Salaita describe how dispersing a fluid containing thousands of electrically-charged microscopic beads or spheres made of silica (glass) across the surface of a DNA microarray and then observing the Brownian motion of the spheres provides measurements of the electrical charges of the DNA molecules. These measurements can in turn be used to interrogate millions of DNA sequences at a time. What's more, these measurements can be observed and recorded with a simple hand-held imaging device — even a cell phone camera will do.

"The assumption has been that no detection technique could be more sensitive than fluorescent labeling, but this is completely untrue, as our results have plainly demonstrated," said Groves. "We've shown that changes in surface charge density as a result of specific DNA hybridization can be detected and quantified with 50-picometer sensitivity, single base-pair mismatch selectivity, and in the presence of complex backgrounds. Furthermore, our electrostatic detection technique should render DNA and RNA microarrays sufficiently cost effective for broad world-health applications, as well as research."



FURTHER READING
Nature biotechnology paper: Electrostatic readout of DNA microarrays with charged microspheres

DNA microarrays are used for gene-expression profiling, single-nucleotide polymorphism detection and disease diagnosis1, 2, 3. A persistent challenge in this area is the lack of microarray screening technology suitable for integration into routine clinical care4, 5. Here, we describe a method for sensitive and label-free electrostatic readout of DNA or RNA hybridization on microarrays. The electrostatic properties of the microarray are measured from the position and motion of charged microspheres randomly dispersed over the surface. We demonstrate nondestructive electrostatic imaging with 10-m lateral resolution over centimeter-length scales, which is four-orders of magnitude larger than that achievable with conventional scanning electrostatic force microscopy. Changes in surface charge density as a result of specific hybridization can be detected and quantified with 50-pM sensitivity, single base-pair mismatch selectivity and in the presence of complex background. Because the naked eye is sufficient to read out hybridization, this approach may facilitate broad application of multiplexed assays

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June 26, 2008

Wired Magazine has positive SENS coverage

Wired magazine has a positive article on Strategies for Engineered Negligible Senescence (SENS) and Aubrey deGrey

Digg that article here

Other researchers have also found some success pursuing similarly structured research programs. For example, late last year, the Buck Institute for Age Research received $25 million from the National Institutes of Health to establish a home for the "new scientific discipline of geroscience." The new field, and its research institute, are dedicated to proactively fighting aging with researchers from a dizzying array of fields.

In research that will first be presented on Friday at the conference, Methuselah-funded scientists will demonstrate a proof-of-concept experiment for using bacterial enzymes to fight atherosclerosis, or the hardening of the arteries. That's an idea that de Grey has been pushing for years.


Gandhi describing his critics,
1. they ignore you
2. then they laugh at you
3. then they fight you
4. then you win

The Fourth Stage of SENS and Aubrey deGrey

"In perhaps seven or eight years, we'll be able to take mice already in middle age and treble their lifespan just by giving them a whole bunch of therapies that rejuvenate them," de Grey said. "Gerontologists all over, even my most strident critics, will say yes, Aubrey de Grey is right."

Even as he imagines completing Gandhi's fourth step, de Grey always keeps his eye on the ultimate prize -- the day when the aging-as-disease meme reaches the tipping point necessary to funnel really big money into the field.

"The following day, Oprah Winfrey will be saying, aging is a disease and let's fix it right now," de Grey said.

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May 20, 2008

Gene therapy advance for safer, cheaper and more efficient procedure and Extinct Tiger gene revived

Replacing one amino acid on the surface of a virus that shepherds corrective genes into cells could be the breakthrough scientists have needed to make gene therapy 30 times more efficient. Gene therapy will be a more viable option for treating genetic diseases such as hemophilia. The discovery could be the solution to a problem that has plagued researchers and doctors using AAV as a gene therapy vector — how to administer enough of the gene-toting virus to yield a therapeutic benefit without triggering an attack from the body’s immune system.


A two-week-old mouse fetus expresses the DNA of the extinct Tasmanian Tiger by developing cartilage, shown in blue. So a hybrid of a mouse and and extinct animal.

This is the realization of many movies and TV shows: Jurassic Park, Manimal, Aliens IV, South Park, Island of Dr Moreau and many more

In separate news, DNA from an extinct Tasmanian Tiger has been resurrected in a live animal (mouse) for the first time. The genetic material, extracted from the extinct Tasmanian tiger, proved functional in mice.


In addition to being more efficient, the new version of AAV could also prove to be more economical, Srivastava said. Current gene therapy trials are expensive because scientists must administer so much of the vector containing the therapeutic gene to see results. Using the new vector, scientists could potentially scale back to using as little as 100 billion particles instead of 10 trillion, Srivastava said.

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May 12, 2008

Accurate biochips for comprehensive disease screening


Biochips contain grids of small wells or "dots," each of which contains a protein, antibody or nucleic acid that can bind to a target antigen or DNA sequence.

New biochips can detect cancers and other diseases accurately before symptoms develop.

Why does this matter ? Early detection can have a large impact on survival rates. Breast cancer detected at stage 0 has a 100% survival rate after 5 years. Those who are detected at stage 4 have a 20% survival rate after 5 years. So if everyone had good and accurate and regular disease screening then no one would die of breast cancer even if treatments do not improve. We can already save everyone who has stage 0 breast cancer. This would save 502,000 lives worldwide every year.

Lung cancer five year survival rates
Stage 0 70-80%
Stage I 50%
Stage II 30%
Stage III 5-15%
Stage IV <2%

Detecting everyone at Stage 0 instead of later stages would reduce 1.3 million deaths per year from lung cancer by nearly 1 million people.

Stomach cancer has similar survival statistics as lung cancer

For liver cancer it drops from 30-60% for early detection down to less than 5%

The 2-D fractionation process creates 960 separate protein fractions, which are then arranged in a single biochip containing 96-well grids. Eprogen scientists then probe the microarrays with known serum or plasma "auto-antibodies" produced by the immune systems of cancer patients. By using cancer patients' own auto-antibodies as a diagnostic tool, doctors could potentially tailor treatments based on their personal autoantibody profile

Though the analysis of a sample on a biochip can take 30 minutes, scientists can have much more confidence in the accuracy of the diagnosis, according to Schabacker. "Biochips give us the ability to run a test that allows your doctor to figure out exactly what you're suffering from during the time that you're in his or her office," he said. By adding just a few more drops to the chip's array, Schabacker claimed, lab technicians could test for a whole slate of biotoxins and especially virulent diseases from the plague to smallpox to anthrax. Other infections, such as those caused by Multidrug-Resistant Tuberculosis (MDR-TB) and the often deadly Methicillin-resistant Staphylococcus aureus (MRSA), can be quickly diagnosed with biochips like Akonni's TruArray assay, according to Daitch.

"The unique advantage offered by the TruArray platform lies in the fact that we can screen a single sample for multiple viral and bacterial infections at the same time," said Charles Daitch, Akonni's president and CEO. "Soon, doctors will no longer need to order as many expensive and time-consuming tests, and can instead obtain accurate diagnoses that will enable them to quickly provide their patients with targeted treatment strategies."



Computer algorithms decode the dot pattern produced by the biochip, calculate the statistical likelihood of each possible infection and provide this information to the doctor.


FURTHER READING
Cancer deaths in the USA dropped to 553,888 in 2004, down from 556,902 in 2003 and 557,271 in 2002, the Cancer Society found.

In 2005, 7.6 million people died of cancer worldwide according to the World Health Organization.

Cancer is a generic term for a group of more than 100 diseases that can affect any part of the body. Other terms used are malignant tumours and neoplasms.

40% of cancer can be prevented (by a healthy diet, physical activity and not using tobacco).

One-fifth of cancers worldwide are due to chronic infections, mainly from hepatitis B viruses HBV (causing liver), human papilloma viruses HPV (causing cervix), Helicobacter pylori (causing stomach), schistosomes (causing bladder), the liver fluke (bile duct) and human immunodeficiency virus HIV (Kaposi sarcoma and lymphomas).

lung (1.3 million deaths/year);
Stomach (almost 1 million deaths/year);
Liver (662,000 deaths/year);
Colon (655,000 deaths/year) and
Breast (502,000 deaths/year)

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April 27, 2008

Gene Therapy used to improve the vision of genetically related Blindness

Gene therapy used to the vision of people with a form of blindness called Leber's Congenital Amaurosis This seems to be the beginning of being able to successfully correct or alter function that is genetically based in adults.

The procedure was safe and effective

Two of the volunteers who could only see hand motions were able to read a few lines of an eye chart within weeks.

One of the treated patients: Steven Howarth said he used to rush home from school because he was worried about getting around in the dark, according to remarks issued by the university. "Now, my sight when it's getting dark or it's badly lit is definitely better. It's a small change — but it makes a big difference to me," said Howarth, who lives in Bolton, near Manchester. After the injection last July, Howarth said his eye felt like sandpaper. It was better after a week, and his eyesight gradually improved. He was able to negotiate a dimly lit maze in 14 seconds without bumping into any obstacles; before it took him 77 seconds with eight errors.

There were no serious side effects reported in either group.

FURTHER READING
Gene Therapy for Leber Congenital Amaurosis : Leber congenital amaurosis (LCA) is an inherited retinal disease that causes with severe visual impairment in infancy or early childhood. Current research on a gene transfer therapy may offer hope to people with a form of this disease.

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April 21, 2008

Complete epigenome of a plant produced

Life often modifies its genetic material without changing the letters of the genetic code. One of the main ways this is done is through the addition of a chemical unit called a methyl group to a gene. Joseph Ecker of the Salk Institute in La Jolla, California and colleagues have used a new method to sequence the complete "methylome" of the cress Arabidopsis for every letter of its genetic code, giving a far more detailed recipe than prior efforts. So just sequencing the DNA genome is not enough, you have to know what DNA is active and has been de-activated by a methyl group.

The Arabidopsis genome comprises some 120 million DNA bases (3% of the size of the human genome) – so the team has developed open-source software to "browse" the genome and find where methylation is controlling gene expression. The program will be able to track more epigenetic data as it is produced, forming a global resource for collecting and analysing it.


They have already begun using these methods for sequencing of the human methylome."

Ecker says that the team will look into how methylation affects the development of human stem cells as they change into other types of cells.



FURTHER READING
Nutritional Control of Reproductive Status in Honeybees via DNA Methylation

Silencing the expression of DNA methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in newly hatched larvae led to a royal jelly–like effect on the larval developmental trajectory; the majority of Dnmt3 small interfering RNA–treated individuals emerged as queens with fully developed ovaries. Our results suggest that DNA methylation in Apis is used for storing epigenetic information, that the use of that information can be differentially altered by nutritional input, and that the flexibility of epigenetic modifications underpins, profound shifts in developmental fates, with massive implications for reproductive and behavioral status.


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April 18, 2008

Monocytes with nanomagnets for enhanced drug and gene therapy delivery

The technique involves inserting nanomagnets into monocytes - a type of white blood cell used to carry gene therapy - and injecting the cells into the bloodstream. The researchers then placed a small magnet over the tumour to create a magnetic field and found that this attracted many more monocytes into the tumour.

This new technique could also be used to help deliver therapeutic genes in other diseases like arthritic joints or ischemic heart tissue.
Better targeting of gene therapy would be helpful for gene therapy for transhuman performance enhancement as well.


Though the concept of magnetic targeting for drug and gene delivery has been around for decades, major technical hurdles have prevented its translation into a clinical therapy. By harnessing and enhancing the monocytes' innate targeting abilities, this technique offers great potential to overcome some of these barriers and bring the technology closer to the clinic.

The team are now looking at how effective magnetic targeting is at delivering a variety of different cancer-fighting genes, including ones which could stop the spread of tumours to other parts of the body.

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April 17, 2008

$100 genome sequencing possible by 2012


MIT Technology Review looks at a process for sequencing DNA that could bring the cost down to $100 for a whole genome within 5 years (by 2012) and work on long sequences of DNA. The new method will also allow reading of long sequences of DNA. Small structural changes in DNA, such as deletions or inversions of short sequences, play a significant role in human variability which are tough to find with short DNA reads. Longer reads will also allow scientists to look at collections of genetic variations that have been inherited together, known as haplotypes. Recent research suggests that in some cases, maternal or paternal inheritance can impact the severity of the disease. The project funding runs to Oct 31, 2012.

Previous article on falling prices of genome sequencing. $60,000 today and maybe $5000 by end of 2008.

I had previous coverage of this back in Oct 2007 when the money was first awarded.

Complete Genomics aims to speed the process by detecting entire "words," each composed of five DNA letters. Drmanac likens the technology to Google searches, which query a database of text with keywords. Further speeding up the process with novel chemistry and advances in nanofabrication, the companies will develop a device that can simultaneously read the sequence of multiple genomes on a single chip.


To accomplish the new sequencing, scientists first generate all possible combinations of five-letter DNA segments, given the four letters, or bases, that make up all DNA. These segments are labeled with different types of fluorescent markers and added in groups to a single-stranded molecule of DNA. When a particular segment matches a sequence on the strand of DNA to be read, it binds to that part of the molecule. A specialized camera then snaps a picture--the different fluorescent signals indicate the sequence at specific points along the strand of DNA. The process is repeated with different five-letter DNA combinations, until the entire molecule is sequenced. The approach is feasible because of the recent availability of cheap DNA synthesis, making it much more efficient to generate libraries of these DNA segments.

Each DNA molecule will be threaded into a nanofluidics device, made by Philadelphia-based BioNanomatrix, lined with rows of tiny channels. The narrow width of the channels--about 100 nanometers--forces the normally tangled DNA to unwind, lining up like a train in a long tunnel and giving researchers a clear view of the molecule

The big difference from any other approach is that they are looking at physical location at the same time they are looking at sequence information. Sequencing methods currently in use sequence small fragments of DNA and then piece together the location of each fragment computationally, which is more time consuming and requires repetitive sequencing.

BioNanomatrix has already shown that long pieces of DNA--two million letters in length--can be threaded into the channels of existing chips. But now researchers need to develop chips with many more channels, so that multiple genomes' worth of DNA can be sequenced simultaneously.

The main hurdle for Complete Genomics will be to generate fluorescent labels that can be easily and accurately detected.



FURTHER READING
News about Bionanomatrix.

U.S. National Institute of Standards and Technology Advanced Technology Program (NIST-ATP) funding of $8.8 million to develop a system capable of sequencing the entire human genome in eight hours at a cost of less than $100.

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April 04, 2008

Summary and Review of ABC : living to 150

Barbara Walters had a show: Live to 150..Can you do it? It was light on details and touched a lot of the topics in the longevity area.

Alcor, the cryogenics company has their article

ABC has other related articles.

I saw the show. It was a very quick run through of many topics on aging. Aubrey's section was maybe 2 minutes and half of that was him riding a bike and paddling on water. His actual speaking points were a very brief summary of extend life 30 years and then during that time extend it again by 50 years and so on up to 1000 years. No details or even mentioning of SENS. Barbara does describe him as a respected scientist and active and basically a "leader in the field".

They had an extended bit on Advanced Cell Technologies corporation. A company whose stock has tanked. Because they could show video of an articifially created rat heart. They interviewed the CSO. Dr. Robert P. Lanza M.D., 51
Chief Scientific Officer. He predicts hundreds of years of life extension using organ and cell replacement and rejuvenation.

Calorie restriction segment shows practitioners and how they eat.

And then a lot of the show (almost half) is talking about and showing how extending life will be good and fulfilling and shows these active older people enjoying life and how people will have many careers and maybe many partners and maybe older woman will become lesbians because they will live so much longer than men. They also mentioned that 30 years was added to life expectancy in the 20th century.

They also talked about gray power and how boomers and others may retain their positions and power and thus help push the funding and effort towards life extension forward.

I think the more older reporters and journalists that there are on 60 minutes and ABC and other places then the more there will be favorable shows of this type.

FURTHER READING
A facebook discussion

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March 25, 2008

Whole genome sequencing costs continue to fall: $300 million in 2003, $1 million 2007, $60,000 now, $5000 by year end

Several companies are sequencing the human genome for about $60,000 to $100,000 and taking about 4 weeks. Whole genome sequencing could be $5000 or less and take 24 hours or less by the end of 2008. Inexpensive costs that will accelerate the transformation of medicine into personal genomics and personal medicine. Prices are going to keep falling with better nanopore and highly parallel approaches. Easy and widespread differential genetic analysis will provide more and better targets for gene therapy and modification. Inexpensive sequencing also helps speed up and reduce costs with DNA synthesis. They are closely related.
Genome sequencing is part of the overall mastery of the genome. Read it cheap and fast and change it, write it precisely, cheaply and safely and build stuff with DNA using DNA nanotechnology and synthetic biology.

In 2003 - just five years ago - the government-backed Human Genome Project, after 13 years of work, produced the first real data of a human genetic code for $300 million. Applied Biosystems said it had been able to analyse the human genome sequence for a cost of less than $60,000, which is the commercial price for all required reagents needed to complete the project. Using the company's SOLiD System, researchers used the system's capabilities to obtain deep sequence coverage of the genome of an anonymous African male of the Yoruba people of Ibadan, Nigeria, who participated in the International HapMap Project. The system generated 36 gigabases of sequence data in 7 runs of the system, achieving throughput up to 9 gigabases per run, which is the highest throughput reported by any of the providers of DNA sequencing technology.


In February of 2008 Illumina claimed it had sequenced a human genome in less than four weeks for approximately $100,000, which included the cost of paying off the purchase price of the company's $500,000 Genome Analyzer.

The company claimed its method produced a more reliable map of the genome. Both companies sequence the same genome multiple times, but Illumina made twice as many passes as Applied Biosystems, he said.

Illumina, Roche and Applied Biosystems are battling to become the technology of choice in a global gene sequencing market that is expected to reach approximately $850m in the next three years. Danaher Corp., based in Washington, said it shipped its first $150,000 Polonator sequencer this week.

Researchers are evaluating technologies for use in the government-led 1,000 Genome Project unveiled January, 2008. The project seeks to sequence genomes at a cost of about $30,000 each.

Intelligent Bio-Systems, a privately held company in Waltham, Mass., says it will introduce a machine by the end of 2008 that might reduce the cost of a genome to $5,000 and perform that work in 24 hours.

George Church Joined the IBS Scientific Advisory Board January 15, 2007.

IBS has a proprietary, patented DNA sequencing by synthesis (SBS) technology capable of reading out the sequence of DNA with very a high precision, rapid pace and low cost. They sequence millions of sequences in parallel on a chip.

In this process the DNA is first broken into fragments, amplified, attached to a DNA sequence primer, then affixed as a high-density array of spots onto a glass chip. To read out the sequence of each of the spots, the array of fragments is first subjected to reagents containing uniquely engineered DNA bases that include a removable fluorescent dye and an end cap. These bases attach themselves (Extend) to the end of the growing strand of DNA in accordance with the base on the complementary strand. The array is scanned by a high-resolution electronic camera (Measure) and the fluorescent output of each of four dye colors at each array position is measured and recorded. The color indicates which base (A, C, G or T) was just incorporated in the DNA fragment in the previous step. Finally, the array is exposed to cleavage chemistry (Cleave) to break off the fluorescent dye and end cap that will now allow additional bases to be added. The Extend, Measure and Cleave cycle is then repeated


UPDATE:
the federal government has awarded about 35 grants totaling $56 million to companies and universities for development of technology that could put the $1,000 genome sequence within reach.

Pacific Biosciences has received $6.6 million from that program.

The nonprofit X Prize Foundation, meanwhile, is offering $10 million to the first group that can sequence 100 human genomes in 10 days, for $10,000 or less per genome. Six companies or academic groups — although not PacBio — have signed up for the competition so far. Some contestants say that they might try for the X Prize as early as next year (2009) and that the $1,000 genome is as little as three years away.

The industry has long been dominated by Applied Biosystems, which sold hundreds of its $300,000 sequencers to the publicly financed Human Genome Project and to Celera Genomics for their sequencing of the first two human genomes, which were announced in 2000.

Read More...

March 24, 2008

Biosensing nanoscale device to revolutionize health screenings

One day soon a biosensing nanodevice developed by Arizona State University researcher Wayne Frasch may eliminate long lines at airport security checkpoints and revolutionize health screenings for diseases like anthrax, cancer and antibiotic resistant Staphylococcus aureus (MRSA)

Frasch works with the enzyme F1-adenosine triphosphatase, better known as F1- ATPase. This enzyme, only 10 to 12 nanometers in diameter, has an axle that spins and produces torque.


What Frasch and his colleagues show is that the enzyme can be armed with an optical probe (gold nanorod) and manipulated to emit a signal when it detects a single molecule of target DNA. This is achieved by anchoring a quiescent F1-ATPase motor to a surface. A single strand of a reference biotinylated DNA molecule is then attached to its axle. The marker protein, biotin, on the DNA is known to bind specifically and tightly to the glycoprotein avidin, so an avidin-coated gold nanorod is then added. The avidin-nanorod attaches to the biotinylated DNA strand and forms a stable complex.

When a test solution containing a target piece of DNA is added, this DNA binds to the single complementary reference strand attached to the F1-ATPase. The DNA complex, suspended between the nanorod and the axle, forms a stiff bridge. Once ATP is added to the test solution, the F1-ATPase axle spins, and with it, the attached (now double-stranded) DNA and nanorod. The whirling nano-sized device emits a pulsing red signal that can then be detected with a microscope.

According to Frasch, the rotation discriminates fully assembled nanodevices from nonspecifically bound nanorods, resulting in a sensitivity limit of one zeptomole (600 molecules). Simply put, if it's not moving and flashing, it simply isn't relevant.

Moreover, Frasch says, �Studies with the F1-ATPase in my laboratory show that since it can detect single DNA molecules, it far exceeds the detection limits of conventional PCR [polymerase chain reaction] technology.

Such a detection instrument based on the F1-ATPase enzyme would also be faster and more portable, he adds.

With support from Science Foundation Arizona (SFAz), Frasch will transfer his work from the bench to biotech, through establishment of a local company that utilizes the nano-sized F1-ATPase to produce a DNA detection instrument.

A prototype of the DNA detector is already in development. It is roughly the size of a small tissue box. Sampling would be as simple as taking a swab from an infected wound or a piece of baggage, dissolving it in a solution and placing a drop on a slide bearing reference F1-ATPases and their nanorods. Once in the instrument, red blinking signals emitted by rotating nanorods would let a computer know there's trouble, literally, in a flash.


RELATED NEWS: A One-Step Homogeneous Immunoassay For Cancer Biomarker Detection Using Gold Nanoparticle Probes Coupled With Dynamic Light Scattering
The early detection of cancer can significantly improve the treatment and survival rate of cancer patients. As tumors develop, the cells, tissues and organs can increase or decrease the release of certain chemicals in the circulatory system. These specific chemicals are called biomarkers. Some of these biomarkers have been approved by FDA for the in-vitro diagnosis of different types of cancer. A well known example is the test of PSA (prostate specific antigen) level for prostate cancer detection. A total PSA level of 4 ng/mL is generally considered as a normal threshold, and when this value exceeds 10 ng/mL, the chance of prostate malignancy is increased substantially.

The nanoDLSA immunoassay is fast, highly sensitive, accurate, and extremely easy to conduct. It requires a much smaller amount (at least 100 times less) of blood samples and antibody probes to conduct the assay compared to ELISA. The cost reduction of nanoDLSA compared to other immunoassays is tremendous. Because of the minute amount of sample that is required by nanoDLSA, it is possible to conduct the detection and measurement of one or multiple cancer markers from a single drop of human blood sample using this new immunoassay technology. The goal of this research group is to develop a fully automated system that can be placed in supermarkets, pharmacy stores, hospitals, and clinics for the general public to test their cancer marker levels as frequently as necessary at affordable prices. The biomarker level history obtained from each individual will provide invaluable information to medical doctors for the early screening and diagnosis of cancer. Equally important, such frequent testing is also critical for cancer patients whose cancer marker levels need to be analyzed constantly to monitor the treatment effect and the recurrence of cancer.


RELATED READING
USB stick genetic testing device for $10 or less.

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March 09, 2008

MIT cell sorting system

MIT has developed a simple, inexpensive system to sort different kinds of cells a process that could result in low-cost tools to test for diseases such as cancer, even in remote locations.

The method relies on the way cells sometimes interact with a surface (such as the wall of a blood vessel) by rolling along it. In the new device, a surface is coated with lines of a material that interacts with the cells, making it seem sticky to specific types of cells. The sticky lines are oriented diagonally to the flow of cell-containing fluid passing over the surface, so as certain kinds of cells respond to the coating they are nudged to one side, allowing them to be separated out.

Cancer cells, for example, can be separated from normal cells by this method, which could ultimately lead to a simple device for cancer screening. Stem cells also exhibit the same kind of selective response, so such devices could eventually be used in research labs to concentrate these cells for further study.


Normally, it takes an array of lab equipment and several separate steps to achieve this kind of separation of cells. This can make such methods impractical for widespread screening of blood samples in the field, especially in remote areas. �Our system is tailor-made for analysis of blood,� Karnik says. In addition, some kinds of cells, including stem cells, are very sensitive to external conditions, so this system could allow them to be concentrated with much less damage than with conventional multi-stage lab techniques.

Now that the basic principle has been harnessed in the lab, Karnik estimates it may take up to two years to develop into a standard device that could be used for laboratory research purposes. Because of the need for extensive testing, development of a device for clinical use could take about five years, he estimates.

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February 20, 2008

Lasers could used to scan for a broad range of disease and health Biomarkers


Laser light can be used to detect molecules in breath that may be markers for diseases like asthma or cancer.

Although it has yet to be tested in clinical trials, a new apparatus may allow doctors to screen people for certain diseases simply by sampling their breath, according to JILA, a joint institute of the National Institute of Standards and Technology (NIST) and the University of Colorado (CU-Boulder).

Known as optical frequency comb spectroscopy, the method is powerful enough to sort through all the molecules in human breath and sensitive enough to distinguish rare molecules that may be biomarkers for specific diseases, said Ye.


When many breath molecules are detected simultaneously, highly reliable, disease-specific information can be collected. Asthma, for example, can be detected much more reliably when carbonyl sulfide, carbon monoxide and hydrogen peroxide are all detected simultaneously with nitric oxide.

While current breath analysis using biomarkers is a noninvasive and low-cost procedure, approaches are limited because the equipment is either not selective enough to detect a diverse set of rare biomarkers or not sensitive enough to detect particular trace amounts of molecules exhaled in human breath.

"The new technique has the potential to be low-cost, rapid and reliable, and is sensitive enough to detect a much wider array of biomarkers all at once for a diverse set of diseases," Ye said.

To test the technology, Ye's team had several CU-Boulder volunteer students breathe into an optical cavity -- a space between two curved mirrors -- then directed sets of ultrafast laser pulses into the cavity. As the light pulses ricocheted around the cavity tens of thousands of times (covering a distance of several kilometers by the time it exited the cavity), the researchers determined which frequencies of light were absorbed, indicating which molecules -- and their quantities -- were present by the amount of light they absorbed.

The remarkable combination of a broad spectral coverage of the entire comb and a sharp spectral resolution of individual comb lines allows them to sensitively identify many different molecules, Ye said. They detected trace signatures of gases like ammonia, carbon monoxide and methane from the samples of volunteers. In one measurement, they detected carbon monoxide in a student smoker that was five times higher compared to a nonsmoking studen.

There is a podcast on this research

The university of Colorado podcast list is here

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February 11, 2008

15 proteins in urine are biomarkers for spotting coronary artery disease (CAD)

A set of 15 proteins found in urine can distinguish healthy individuals from those who have coronary artery disease (CAD), a new study has found.

Coronary artery disease is the most common type of cardiovascular disease, occurring in about 5 to 9% (depending on sex and race) of people aged 20 and older.

In 2001, the death rate from coronary artery disease was 228 per 100,000 white men, 262 per 100,000 black men, 137 per 100,000 white women, and 177 per 100,000 black women. Over 1 million deaths per year worldwide.

Due to the ease of obtaining samples, urinary protein analysis is emerging as a powerful tool to detect and monitor disease.

The researchers next examined how predictive their protein panel was and found it could identify the presence of CAD 83% of the time. The panel had a sensitivity of over 98%, which means the test produced almost no false positives and thus inaccuracies are primarily misdiagnosing CAD individuals as healthy. The researchers also observed that the protein signatures of CAD individuals became more normal after exercise, suggesting these biomarkers can be used to both help diagnose CAD and monitor the progress of treatment.


FURTHER READING
A USB stick size device has been created for genetic screening in minutes for tens of dollar A similar cost device seems possible for screening for the proteins that identify coronary artery disease.

This is another major piece in the vision that I and many others have to transform public health with widespread use of frequent biomarker tracking to identify people in the early stages of disease or those just with the increased risk factors and transform medicine to cheaper prevention of disease development

This should also be used to change drug approvals by identifying earlier when a drug is having effect with improved biomarkers.

More papers by Anna Dominiczak

Cardiovascular disease statistics

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February 04, 2008

Reviewing my predictions on the future and recent Gartner predictions

Here is another update to my March 2006 technology predictions.

Prediction: Real-time biomarker tracking and monitoring 2008-2012

Progress: Cheap less than $100 USB gene tester

Old mockup of the cheap gene tester. The device is now much smaller than size of a shoe-box (USB stick size) with the optics and supporting electronics filling the space around the microchip.

Prediction: Real-time personalized disease treatment 2008-2012

Progress: The above gene tester can be used to test within minutes for adverse drug reactions which are a major problem in health care. By running a quick genetic test on a cancer patient, for example, doctors might pinpoint the type of cancer and determine the best drug and correct dosage for the individual.




Prediction: 80-200mpg cars - mainstream, batteries, ultracapacitors 5-10 times better 2008-2012

Progress:
Australian ultraBattery has a life cycle that is at least four times longer and produces 50 per cent more power than conventional battery systems. It’s also about 70 per cent cheaper than the batteries currently used in HEVs

EEStor ultracapacitor expected for mid-2008 and will be used in Zenn Motors electric and hybrid cars


AFS Trinity has what it calls Extreme Hybrid (XH) technology which employs a proprietary dual energy storage system that combines Lithium-Ion batteries and ultra capacitors with control electronics. They showed their 150 mpg hybrid SUV at the North American International Auto Show (NAIAS) in Detroit.

Prediction: Customized cells 2010-2014

Progress: Synthetic life- custom cell with completely synthesized DNA likely in 2008.
A 582,970 base pair sequence of DNA has been synthesized.

Prediction: Gecko mimicing wallcrawling suits for military and enthusiasts 2008-2012

Researchers at the University of California, Berkeley, have developed an adhesive that is the first to master the easy attach and easy release of the reptile's padded feet. The material could prove useful for a range of products, from climbing equipment to medical devices.

Prediction: Wireless superbroadband (50-1000Mbps) 2009-2012

Progress:
List of deployed wimax networkks

Whitespace modems continue to be tested and could provide 50-100Mbps or faster speed

More on whitespace modems

Prediction: Fiber to the home (100Mbps-1000Mbps) 2010-2015

Progress: Various groups in the USA are pushing for national broadband policy to be passed in 2008 to encourage 100Mbps or faster connections Japan has 93.7 Mbps average download speeds in October 2007.

Fiber to the premises deployment history by country at wikipedia

Prediction: Advanced plastic circuits, computing, monitors and energy gathering-walls, roofs, desktops 2009-2012

Progress: Printable electronics catching up to speed of CMOS electronics. Several of the technologies are suitable for printing electronic displays in a method similar in speed and cost to how newspapers are made now. (reel to reel printing of large areas)

Prediction: One billion digital video cameras posting online realtime; personal privacy is history 2008-2012

Progress: Over 1.24 billion cellphones will be shipped in 2008. Over 1 billion of those will be camera phones. As of Q2 2007, there are over 131 million UMTS users (and hence potential videophone users), on 134 networks in 59 countries. Camcorder sales are 4.5 million to 5.8 million per year in the United States Camcorders, are under 100 million total shipped as of 2007 The key to this prediction is if most new cellphones shift over to videophones. As over one billion cellphones will ship in 2009.

Prediction: 10 petaflop computer 2012-2013

Progress:
The Blue Gene/P machine at Argonne is supposed to reach one petaflop — 1 quadrillion sustained operations per second — in 2008. It should have a peak speed of three petaflops by the end of 2008.

Turek said IBM's goal was 10 petaflops by 2011 and 20 petaflops by 2017. The Japanese have announced their intent to reach 10 petaflops by 2012.


The Sun Constellation compute speed is estimated at 1.7 petaflops, and it will store up to 10 petabytes of data.

Fujitsu expects to build a supercomputer that can perform 3 quadrillion calculations per second, or petaflops, in 2011

Prediction: Optical interconnects connect CPUs directly at 100 Gbps+ 2012-2018

Progress: IBM reveals core-to-core optical dream in progress.

IBM researchers have created a modulator that's one hundred to a thousand times smaller than other prior modulators and is theoretically capable of using light pulses to transmit data between cores, rather than relying on traditional wires. Chip-level optical routing would allow cores to communicate much faster than even the best wired connection (IBM estimates its nanophotonic technology would be 100 times faster) and would almost certainly eliminate any bandwidth-related bottlenecks within a single core.



Prediction: DNA nanotechnology creates nanotools and parts 2010-2015


Progress: Synthetic biology is making DNA for mechanical and electronic purposes DNA to assemble millions of three dimensional nanoparticles, and all molecular programmable DNA construction.

Progress: Two artificial DNA "letters" that are accurately and efficiently replicated by a natural enzyme have been created by US researchers. Adding the two artificial building blocks to the four that naturally comprise DNA could allow wildly different kinds of genetic engineering, they say. This combines with the previous articles about using DNA to assemble millions of three dimensional nanoparticles, being able to synthesize strings of DNA over 500,000 base pairs long and all molecular programmable DNA construction.

Prediction: Protein engineering creates artificial ribosome