By Steven Salzberg

from GeneWatch 28-3 | Oct-Dec 2015


Humans are on the verge of developing the technology to rewrite our own genetic code. It's now a question of "when," not "if."

Over the past decade, three new technologies for DNA editing have been developed. First there was a method based on genes known as zinc finger nucleases (ZFNs), which can cut DNA and allow a scientist to insert a new piece of genetic material. The patent on zinc finger technology is owned by Sangamo BioSciences, which licenses it out and is also using it to develop novel treatments. For example, Sangamo is developing a treatment for HIV/AIDs, already in Phase 2 trials, that uses ZFNs to edit the gene CCR5, a critical receptor that HIV needs to infect immune cells. If successful, the improved CCR5 gene could prevent and even cure infection.

Zinc fingers work, but they are tricky and expensive. A much-improved technology is based on an invention due to bacteria: Transcription activator-like effector nucleases, or TALENs. These genes are used by certain bacteria to help them infect plants. I led a bacterial genome project about a decade ago in which we sequenced several species of a plant pathogen called Xanthomonas oryzae, which is one of the primary sources of TAL genes.

It turns out that TALENs can be used to edit DNA too, just like zinc fingers. TALEN technology is much faster and cheaper, and many scientists quickly adopted it because of these advantages. It's available in a kit from Life Technologies, allowing scientists to edit the genomes of yeast, plants, insects, and mammals (including humans).

The latest and hottest technology is called CRISPR, another bacterial invention. In the early 2000's, a variety of genome scientists noticed that some bacterial genomes contained long stretches of repetitive DNA interspersed with bits of viral DNA. This was a mystery until scientists determined, in 2007, that the bacteria were using the viral DNA as an immune system: after capturing a bit of the virus's DNA, the bacteria was protected from infection by that virus.

Bacteria use the CRISPR system to recognize a virus and chop it up, thereby preventing it from killing them. In 2012, two teams of scientists including Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang figured out how to use CRISPRs to edit genomes. (Within the scientific community, there is a fierce battle going on over who first invented this technology. Suffice it to say that the original inventors were microbes, not people.)

CRISPRs are even better than TALENs: according to one recent review, they are "simple, inexpensive, easily programmed and ridiculously efficient."

The scientific community has mapped the human genome and determined the functions of many of our genes. This enterprise still has a long way to go, but we know our genetic code, and we're developing the methods to figure out how to alter genes to correct genetic defects, to help our immune systems fight disease, and to prevent cells from becoming cancerous. It's only a matter of time before we find ways to adjust our genes to improve our vision, hearing, physical endurance, and other traits.

One more critical piece of the puzzle, before we can custom-design humans, is the ability to turn a human cell into a pluripotent stem cell, one that can turn into a germline cell (an egg or a sperm cell). This technology too is rapidly maturing: scientists have already cloned mammals using adult cells that they turned back into stem cells.

Thus the two main pieces are in place: we can create germline cells, and we can edit our genome. It won't be long before someone puts the two together. History teaches us that once a technology appears, we can't put it back in the box. Genome editing is here, and it has tremendous potential to cure diseases and reduce human suffering. It also offers us the opportunity to improve our own genetic code. Given the choice to throw away our glasses and acquire the visual acuity of an eagle, how many people would say no? How about genes that will keep our arteries free of cholesterol until past the age of 100? Or genes that will prevent dementia and Alzheimer's, the greatest scourges of advanced old age?

No doubt many people are disturbed at the thought of editing our own DNA. Clearly we need to be careful how we employ this powerful new technology, but denying or ignoring it is not the answer. Genome editing is here, and human bioenhancement will not be far behind.

Steven Salzberg, PhD, is Bloomberg Distinguished Professor of Biomedical Engineering, Computer Science, and Biostatistics at Johns Hopkins University.

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