CRISPR: The Technology Behind Human Embryo Editing

The startling research paper detailing the first-ever attempt to edit the genome of human embryos has aroused a great deal of interest and some alarm, but the nature of the DNA editing technique, known as CRISPR, is not so widely known.

Also not so widely known is the technique’s peculiar history, which shows again how discoveries in pure science can lead to amazing technological breakthroughs.

The CRISPR story began when biologists, exploring the DNA of certain types of bacteria, realized that microbes, like people, can build up their own immune systems against foreign viruses.

It was in the late 1990s, according to Science Magazine’s Elizabeth Pennisi:

…that biologists discovered unusual patterns in the bacterial DNA, in which a sequence of DNA would be followed by nearly the same sequence in reverse, then 30 or so seemingly random bases of “spacer DNA,” and then a repeat of the same palindromic sequence, followed by a different spacer DNA. A single microbe could have several such stretches, each with different repeat and intervening sequences. This pattern appears in more than 40% of bacteria and fully 90% of microbes in a different domain, the archaea, and gives CRISPR its name. (It stands for clustered regularly interspaced short palindromic repeats.)

At the time, many researchers assumed that the ‘spacer’ sequences were junk, but in 2005, Pennisi notes, three different teams reported that spacer DNA often matched the sequences of different viruses. This suggested that the book-ending repeat sequences in the bacterial genome played a role in bacterial immunity.

Further study revealed that bacteria take up the viral DNA, then store it as a sort of template for the bacteria’s RNA to use in order to neutralize new invading viruses whose DNA is a match.

How did this process work? In brief, once the bacterial cell was invaded, it manufactured RNA from its stored virus code and this would be transported, or guided, to the matching viral DNA by particular enzymes in the cell –the most efficient one is known as Cas9, which has the ability to cut and re-combine DNA.

A short video here provides a good animation of how the process works.

In just the past three years, scientists have figured out how to use the same system to find and cut —and replace–sequences of DNA in human cells.

In terms of gene therapy, the clinical promise of CRISPR is huge. As U.C. Davis stem cell researcher Paul Knoepfler told me, people suffering from blood diseases like Beta thalassemia and leukemia, could have their blood cells’ DNA fixed with the CRISPR technology, and used to grow healthy blood cells to replace the faulty ones.

But what about fixing genetic defects in advance?

Several researchers have already used CRISPR to edit the genomes of mouse embryos and produced healthy specimens.

It was really just a matter of time, scientists said, before someone would try the same technology on human embryos. And while last week’s paper had long been expected (as was also the team’s initial negative results), they believe many other teams are already working to improve the CRISPR approach so that very soon IVF embryos carrying potential disease causing genes can be successfully edited to avoid them.

This promises to be an exciting new frontier for scientists–but the bioethical implications will be daunting, especially if CRISPR can be employed to enhance human traits.

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Source: Forbes Health