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January 13, 2013

Large scale genetic modification for healthier people and longer lives with significant impact over the next 3 to 15 years

Beneficial gene therapy for HIV cure in phase 2 human trials

There is a phase 2 clinical trial to genetically modify t-cells to create immunity to HIV. Tim Brown, the famous "Berlin patient" and first person cured of HIV. Brown's visit and Sangamo's clinical trial results draw attention to human gene therapy with beneficial mutations. In Sangamo's case, its scientists generate mutations in the CCR5 gene in human CD4 T cells that conferred resistance to HIV-1, the most common strain of the virus. Brown was cured when he received donated CD4 T cells with a naturally occurring CCR5 mutation. The company Sangamo has touted results at the one-year clinical trial endpoint: in five of nine subjects, CD4 T cell counts persisted a year after infusion at greater than 500 cells/mm3, the accepted threshold for initiation of HAART therapy. It might be three years to get past the clinical trial phase for this approach.

CRISPR will allow large scale genetic editing for a lot of beneficial mutations.
Mutations for viral immunity, longevity and other mass changes to stem cells extracted and modified and then reintroduced to the body.

Thousands of changes could be made and then copied for millions of stem cells.

This method could be used for a transhuman future with radical life extension and other genetic and epigenetic changes.

George Church described these goals in his latest book Regenesis and a Discovery Magazine article.

Some people are almost transhuman now

* Rare double mutants in the myostatin gene have more lean muscle and less body fat
* those with the LRP5 gene have extra strong bones (like the real version of the Bruce Willis movie Unbreakable character
* Those with the PCSK5 gene have 88 percent lower coronary disease
* Those with double CCR5 genes are HIV resistant
* Those with double FUT2 are resistant to stomach flu

More muscle and stronger bones can be used to counter frailty in the elderly.

1% of a total population – or 10% of a disabled population – need wheelchairs, i.e. about 71 million people worldwide. In 2003, it was estimated that 20 million of those requiring a wheelchair for mobility did not have one.

About 7% of persons older than 65 years are frail, and that the occurrence of frailty increases with age and may exceed 45% after age 85. By 2050, one in six people will be over the age of 65. This will be about 1.5 billion people. If 7% of them were frail that would be 105 million people.

Coronary disease is the cause of about 25% of deaths in developed countries.

A Dopamine gene might be a factor in longevity (seems to have 5-9% boost for longevity of mice

Identifying all of the unambiguously beneficial genetic changes for people and applying them to different tissue / stem cells and introducing them into people should definitely

- radically improve immune systems (easy to access immune systems, white blood cells, t-cells). Genetic engineering supercharged equivalent of vaccination. Vaccines alter and educate our immune system.
- easy to access blood
- could alter some of the 6 pounds of bacteria in our guts to alter out internal ecosystem



Resistance to all Viruses

E. Coli has been modified to have mirrored handedness DNA for many of the codons

Indeterminant Lifespan

George Church is a giant in gene sequencing, synthetic biology and DNA science. In the October, 2012 Discover Magazine, George Church teases with some ideas he has for achieving physical immortality (indeterminant lifespans) via Synthetic biology.

George's idea is to bring in sections of DNA from exotic organisms or genes that are rare for humans to enable all people to have desired genetic capabilities. He describes capabilities such as immunity to all viruses and cellular immunity to radiation and creating immunity to diseases.

They are working to sequence and determine the genetic basis for long lived animals and humans and determine how to engineer longer lived people.

They are working on approaches to rejuvenate different kinds of cells including the neurons of the brain.

Detailed review and information on Regenesis book

Newbooksinbrief has a detailed review and explanation of the George Church and Ed Regis Book Regenesis

The Future of Biomaterials and Engineered Organims: Mirror Biology

Synthetic biology not only holds the promise of allowing us to mass produce all manner of fuels, plastics and other materials (including, as we shall soon see, drugs and vaccines), it also holds the promise of increasing our current repertoire of the building blocks of matter, thus vastly increasing the variety of substances and materials that we can produce.

As mentioned above, the standard amino acids out of which proteins are made (and out of which biological products are produced) is limited to 20. However, this number could potentially be doubled in a fairly straightforward way. This is because all of the amino acids come in one of two possible orientations called ‘handedness’(based on how the molecules that make them up are organized). Biologists can flip the molecular orientation of each amino acid (except glycine, which is symmetrical, and so the same when flipped, thus producing a whole new set of amino acids with different properties. These amino acids could then be used to create new proteins, and hence new biological products. As Church explains, this will “give us access to an entire new world of exotic biomaterials, pharmaceuticals, chemicals—and who knows what else”.

The ‘who knows what else’ come from the fact that flipping the handedness of amino acids could not only be used to create new proteins and biological products, but whole new organisms (mirror organisms, as it were [loc. 530]), including mirror humans! Interestingly, because these mirror humans would be made up entirely of molecules that are opposite-handed to the molecules of regular life-forms, viruses and other pathogens would be unable to read their cells (loc. 534), and so would not be able to infect them. In other words, these mirror humans would be completely immune to viral and other pathogenic diseases


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