Reasons why IMHO, KBLB's silkworms are highly unlikely to have problems due to the removal of the worm silk protein genes that are currently being done with the zinc fingers:
Silkworms have been highly selected for silk production for thousands of years (tens of thousands of silkworm generations) The effect of such long term selection for commercial traits is to cause duplications of the genes for the traits selected for (in this case silk production genes) and to move the functions of the traits selected for away from other functions (i.e.: to different genes).
This happens because genes sometimes get duplicated. Such duplications tend to strengthen the traits the gene codes for (if for hair color, for example, more pigment gets produced so the hair is darker). If a duplicated gene is for one of the traits being selected for, the animal carrying it will be selected (if the trait is beneficial). Over extended time the result is that commercial animals that have been selectively bred for many generations will have duplicate copies of the genes for their most important traits.
Some genes have multiple functions. A mutation may remove one of the functions of a gene without affecting the other(s). When there are duplicate copies of a gene a mutation may cause one copy to lose one of its functions. Because there is another copy of the gene, the trait remains and it is not selected out. Then later another mutation causes a second copy to lose the function that remained in the first gene. The result is that where you started with one gene with two functions you now have two genes each with one of the functions of the original gene but not the other function. From two functions in one gene to two genes each with a different one of the original functions.
Over many generations of selection this process tends to cause the genes for important commercial traits (in silkworm the genes affecting silk production) to become separated from other functions (i.e.: on different genes instead of on the same gene) and often present in multiple copies.
Because of this isolation of function, the removal of the silkworm silk protein gene is unlikely to have any other function than the silk protein itself. That removes most of one of the few possible dangers of the removal of the silkworm silk protein gene.
The gene for spider silk was added to the worms before the removal of the silkworm silk gene is even being attempted. Because of their close similarities it is unlikely that the removal of the worm silk protein will leave a “gap” that the spider silk protein won't fill, but it is possible: for example, some enzyme important to proper folding of the silk protein might have its levels regulated by the presence of the worm silk protein and the molecule that recognizes the presence of the silkworm protein may not recognize the presence of the spider silk protein. That's very unlikely to occur given that the worms have already produced silk containing up to 80% spider silk protein (so if some regulation mechanism needed to recognize the silk protein but didn't recognize the spider version of the silk protein problems would almost certainly already occurred. But even if it did, it could probably readily be worked around: just take the equivalent silk recognition protein in the spider and take the sequence coding for the recognition region of that protein and replace the recognition region sequence of the worm protein with it. There are tools to do all that, and thanks to the zinc fingers doing that genetic modification will also be easy. And since KBLB has 200 spider genes, all related to silk production it's highly likely that it will already have any such genes needed.
There are a few other potential problems, all very unlikely for similar reasons given that the worms have already produced silk with up to 80% spider protein successfully and shown no problems. And there are workarounds available for them as well should they occur.
Bottom line: the removal of the silkworm silk protein genes from the worms is almost certain to be successful the first time given the excellent track record of SGMO and SIAL's zinc fingers. (as noted previously some other researchers have had more difficulty with zinc fingers but, as I described in great detail in a recent post, SGMO/SIAL's zinc fingers have a vastly superior technology and an excellent track record. I also posted a scientific study in a peer reviewed journal of an experiment that showed that zinc fingers work in silkworms and will post it again.
And the successful removal of the silkworm silk protein gene is dead certain to prevent any worm protein from being in any silk produced. It would be physiologically impossible for the worms to produce silkworm silk protein without a copy of the gene for it.
And the removal of the silk worm silk protein is very unlikely (as per the above discussion) to cause any problems with silk production and, even if it does, there is likely to be a workaround available.
If the ZF modifications don't work on the first try that would NOT be a show-stopper. Zinc fingers work the first time most of the time but not 100% of the time. A simple repetition with a possible tweaking of the zinc fingers would likely be successful.
Bear in mind that Kim said to expect results in the fall and, as I discussed previously, this could be a two step two generation process. If so then mid September to mid October would be more like the timing for pure spider silk (although a PR on an intermediate stage/GM would IMHO be highly likely in such a case.)
Nothing, of course, is guaranteed. But in this case the odds are very high for success.
Remember, this is research, something that's never been done before. Anyone who says they KNOW what will happen is either delusional or lying.
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VERY IMPORTANT: One thing must be kept firmly in mind when investing in any company involved in any kind of technological research: There is ALWAYS some possibility of unforeseen problems NO MATTER WHAT FIELD THE RESEARCH IS IN AND NO MATTER WHAT COMPANY IS DOING IT! If that possibility wasn't there then it wouldn't be research!
The answer to that is to
1) do your due diligence and weigh the risks against the potential gains. In this case the risks are relatively small: genetically modified organisms have been used for many years already for the commercial production of products (bacteria, yeasts and progressively into higher organisms) The concept is well proven and the risks are mostly well known. Moreover one generation of worms has already tolerated the insertions - so it a problem arises it should be specific to a particular insertion or deletion and not to the whole principle of doing it. Easy solution would be just leave out inserting that gene (there are 199 more to do the job) but there would be much potential for developing solutions. That is generally the way that research advances and investors should know that problems may arise (that being the very nature of research) but generally they can be dealt with.
2) do NOT a)invest more in any one company than you can afford to lose (with early stage biotechs the potential for reward is great and even a small part of your portfolio can get sizeable gains. But don't put all your eggs in one basket!
do NOT b) invest money that you cannot afford to leave for a long period. (the pace of research is inherently unpredictable and share prices can get dips, sometimes prolonged, due to snags in the research. Often the problem is overcome and the share price bounces right back up but that's no consolation if you needed the money and had to take it out during a dip.
do not even THINK about investing with margin or money borrowed from other sources! With margin you will be forced to sell on dips and lock in the losses. With money from credit cards you're paying 20% per annum premium for investing. that's like running a race wearing a weight belt!
To succeed in investing in technology companies you have to be at home with the idea of accepting risk (that, after all, is what the rewards are paid for!) what you do is to mange it (by diversification and due diligence and keeping up with the news and **finding out what the real significance is** before selling out in a panic!
The litmus test is how well do you sleep at night. If not well maybe you should adjust your approach.
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