Re: Sangamo's significance
That was the hardest part of all to take, IMHO: that the Vegf was successfully upregulated and there were many other conditions for which it would very likely be useful. But doing yet another trial of SB509 for one of them would have been nevertheless a very bad move, if only because of the "politics". EL would have encountered a great deal of resistance had he done that and the SP would almost certainly have suffered greatly. What was needed was a much "safer" target (i.e.: NOT several steps removed in a very complex pathway from a result that was also influenced by many other factors!) The monogentic disorders are exactly such a "safe" target. And the Shire deal gives great financial stability (Shire pays for ALL development costs PLUS unencumbered milestone payments that can be used for other things!).
Treating the monogenetic disorders with zinc fingers are about as good a bet as you'll ever get in biology. We KNOW in some cases (because of many years of experience of treating with replacements) that if you can correct the gene in situ so that it supplies the correct protein IN SUFFICIENT LEVELS that will effectively treat the problem. (And the SB509 trial - which DID accomplish the desired production of the protein - has given some idea of the levels that can currently*1 be accomplished so we are NOT "working in the dark" here! The HIV trials have been establishing that you can treat cells outside the body with zinc fingers and return them without adverse effects and that the altered cells can survive for considerable periods.
In the HIV trials the altered cells produce an altered cell surface receptor (CCR5) which is different from producing a protein that is very active in metabolism. But that HAS been done successfully in mice and there is no reason to expect it won't work in humans.
Hemophilia is undoubtedly one of the first monogentic disorders to be treated because it only requires a very small level of the correct protein to have a very good therapeutic effect. (First pick the low hanging fruit!). From testing the levels that actually are produced they'll get a good idea of which of the other monogentic disorders are likely to be successfully treated. Then on to other monogentic disorders with also very good chances of success, because from long history of treatment, we know what levels of the gene product are needed for good therapeutic results. And those should go far towards establishing both credibility and a solid financial basis.
The next big step would be adding or correcting a gene AND also affecting it's regulation at the same time (and zinc fingers are excellent for that!: it's what they DO naturally! (editing and adding and deleting genes are just things that SGMO has altered them to do). When SGMO has established that it can do that effectively it will have shown it has a high probability (no SURE things in biology!) of being able to treat ANY monogenetic disorder (because you can upregulate the corrected genes to produce enough protein even if you can't add enough of them to do the job without that upregulation). ADDITIONALLY the ability to change regulation could potentially be used on its own to treat many disorders. One "proof of concept" there and you've added another large group of potential targets.
The potential is huge.
*1 very likely, as the technology is developed, they will find ways to achieve higher and higher levels of production (including probably both with and without added regulation IMHO)