Recently, a paper was published in PNAS titled, Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing. It could possibly be one of the most excited papers of the last 10 years and this discovery could be more important than CRISPR. I don’t really know why no one is talking about it.
The main way gene therapy or gene editing occurs is by using a virus. The virus is really good at entering cells and so scientist’s can program it to carry the genes that they want instead of its normal genome. Usually, these viruses cannot replicate inside the cells and so runaway viruses infecting everything doesn’t happen.
AAV(Adeno Associated Viruses) don’t usually edit the DNA or genome of the cell they enter. What they do is add extra DNA to the cell and convince the cell to use this extra DNA. For genetic engineering this is all you need because instead of fixing a gene that is bad in the cell you can just add a good copy. The problem is that the extra gene the virus adds is usually not permanent.
In order to make a change in a cell permanent you need to alter the DNA already in the cell; this is what CRISPR does. The problem with CRISPR is that even though it is one of the best tools we have it isn’t easy to use and deliver to a living organism with lots of cells because there are multiple components(Cas9 protein, gRNA, Template DNA).
In the paper mentioned above, the scientists found that some of these AAVs(there are lots of slightly different ones) could actually edit the DNA already in the cell not just add extra DNA. This is groundbreaking because to edit the DNA already in cells using CRISPR it requires at least two simultaneous viruses to be able to fit all the elements required. Not only that, the editing efficiency of CRISPR is low, generally around 1% but using special tricks can get up to 5%-10%. This new AAV method is greater than 50% and doesn’t require any special tricks.
The interesting thing is that the company that owns the patents to this stuff, Homology Medicines, had their stock price drop after this paper was published in July and I can’t really tell why? Is this method actually viable because if the paper is reproducible it will outperform CRISPR in the clinic easily.