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New technique for in vivo gene modification, more like a CrispR-Cas9 supplement than a replacement



So some are cheerleading a new technique for inducing genetic modification.

The key issue that stands out with this new technique is indicated near the end of that article, it is NOT a permanent process.

First, the claim that the possibility of cancer formation exists with the process of Crispr / Cas9 is true but then the probability of formation is the same for a natural gene silencing operating which are constantly happening over the developmental life cycle of any organism.

That is why it is such an amazing technique to start, the mention of promoter addition as a possible bad thing doesn't make any sense to me (but I may not understand what they mean)...if you want to activate an inserted gene you need a promoter that is the switch essentially...to activate the inserted gene or by being found in a silencing operation is methylated.

In the final analysis to do all the things we want to do.

1) Repair existing genes in vivo (permanently).
2) Add in new genes in vivo (permanently).
3) Remove existing genes in vivo (of course permanently).

Crispr/Cas9 is a single stop solution that co-opts a robust natural system to employ those actions with risks that are comparable to the same actions being done naturally so there is no real disadvantage when you think of it from that perspective. Also, it stands as a multi prong approach...modulation of the associated protein configuration could radically improve specificity and reduce any possible side effects. A paper linked below details ways to extend the technique...it's more a toolkit for gene editing than just a one shot method like TALENS was before it.

I stand by my comment when I first heard of CrispR end of 2012, by 2017 Stockholm is calling Dr. Doudna (one of the principle researchers). It's a done deal.

I compiled a bunch of the seminal papers on the technology in my drive folder for those who haven't done a deep dive:

https://drive.google.com/folderview?id=0B9N6z_bRVUMmSklFbE9Da1hFa0U&usp=sharing

The article that does an excellent job of explaining what the problems are regarding oncogenesis risk and how those can be prevented (I think some have already been tried since this paper was written) are listed.

https://drive.google.com/file/d/0B9N6z_bRVUMmRWhwOHpxc2NhcUE/view?usp=sharing

:The short summary is that oncogenisis is not an inherent problem of the approach assuming it is applied 100% correctly but more a result of not ensuring uniqueness for the desired region of modulation (addition,removal or silencing). This would make sense as if you are trying to target a short sequence out of a strand of billions you need some way to disambiguate that one sequence from the many similar sequences that an improperly specific Cas9 program would produce. That said the authors (including George Church) indicate ways to get around these problems.

In the folder the paper that presented the use of CrispR with Cas9 to be a gene snipping tool is titled:

"Repurposing Crispr as an RNA guided platform for sequence specific control of gene expression"

https://drive.google.com/file/d/0B9N6z_bRVUMmMWU2VmxkdVZpWDg/view?usp=sharing

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