CRISPR’s
by Anonymous Questions | May 7, 2014 11:23 pm
For Dr. KSS[1]:
First a sincere thank you for the most informative and actionable information about the most exciting area of human endeavor.
My question involves CRISPR[2]’s and their potential as a revolutionary gene modification technology.
At this time I can only find a private research firm ”Editas Medicine” that has patents on the technology but there seem to be many companies offering ”gene splicing Kits” for as little as $200-$300.
I am still very interested in Benitec and I just opened a small position in OXBT as well.
Does this technology affect the potential market for Benitec.
Since this is the first time I have sent a request I am not sure how to look for an answer.
I have a hard time with the comment chains because they often seem to go off on tangents, even if the tangents are interesting.
Thanks again for all of your fine work. At my age, 70, studying the info that you so graciously and generously offer keeps me young and looking excitedly toward the future.
Thanks again
- Dr. KSS: https://www.stockgumshoe.com/tag/dr-kss/
- CRISPR: https://www.stockgumshoe.com/tag/crispr/
Source URL: https://www.stockgumshoe.com/2014/05/microblog-crisprs/
log
Hi OP (Questions): I am glad you are reading and participating in our biotech ever-fandango here.
CRISPR technology is getting a lot of attention right now perhaps for the wrong reason: a battle royale between the two women who discovered it, which has now gone into the court system (lawyers, judges and juries are probably not competent vehicles to be reviewing this). What is shaping up now is a basis for a perennial Montague versus Capulet (or Hatfield versus McCoy, if you prefer) feud between the two companies that those two women have split their loyalties and former professional relationship between: Editas Medicine and Crispr Technology, Neither are public; both are VC-funded. Both have promise for eventual relevance in treating human disease, though they are easily 15 years from completing all stages of development to be able to do so and do not at this juncture pose any threat either to Benitec (ddRNAi) or RNAi plays such as Arrowhead, Alnylam, Tekmira, RXII.
Before there were eukaryotes, there were prokaryotes (which abound and are still with us….they are bacteria). Bacteria have always suffered from being vulnerable to continuous attack by phages, viruses, which modify the bacterial genome. We think of the immune system as being a thing in complex multicelled organisms that consists of antibodies and white cells. But perhaps life on earth’s first ever stab at an immune system-like behavior was development of the CRISPR system, a set of proteins via which bacteria could look at the scroll of their own genome, discern where bacteriophage viruses had altered it, and cleanly edit out the mess or disruptions.
Many human diseases are caused by mutations. And I find most people are not clear what that means. Our DNA is our scroll with the recipes for all the proteins that make us. A mutation is when the recipe for one protein is befouled. Usually, however, mutations are not total fouling of the protein sequence script but rather just a single nucleotide error. DNA is a code of adenine, thymine, guanine and cytosine, and one common theme in biology is that it occasionally replaces cytosine (C) erroneously with guanine (G). Most mutations are errors at just one nucleotide, one letter at one position in the code. CRISPR may be a way to edit out that error and replace it with the right letter.
Suppose you have just completed a novel. You remember that in 3-4 places in the novel you used the word “synecdoche”…..only it isn’t a word you use in writing a lot and you actually spelt it “synechdoche” at least twice. And then you are reading an essay or a book and you see the word as it should be spelled. It nags you and you want to fix it, but you do not want to re-read your whole manuscript. (And suppose the word-processing word find and replace function does not exist.) You can program your computer to search the manuscript for all H’s, and when it finds an H preceded by “S Y N E C” and followed by “D O C H E” you can tell it to snip out that H….and leave all other H’s alone. The CRISPR/Cas system is sort of like this: it can scan the genome and everywhere there is an error in a complex context (identified by an accompanying strand of RNA that leads you to the DNA site) it snips out the error and replaces it with normal DNA.
CRISPR was recently used successfully for the first time to cure mice of hereditary tyrosinemia, a genetic liver disease in which the liver does not process the amino acid tyrosine correctly and which can be quite fatal. In mice, this disease owes to a single point mutation, one wrong letter, in the gene for a tyrosine processing enzyme called FAH. An MIT group was able to deploy Cas, mutant RNA and a healthy FAS gene into hepatocytes of affected mice. They were able to accomplishing gene editing in about one out of every 250 hepatocytes (quite inefficient). Since the disease causes affected hepatocytes to die, the gene-edited healthy hepatocytes prevailed, the diseased ones died, and by the time the mice were sacrificed and their livers breadloafed up for scientific analysis, it appeared that about a third of the hepatocytes had the new edited healthy gene.
And this I feel illustrates a problem with the CRISPR method: efficacy or penetration…..when you deploy it in a living system, it does not affect a majority of cells. RNAI and ddRNAi have long since overcome this hurdle. There is still also no proof that it can be trusted to edit only the intended site. If it were to do off-target editing, it could very quickly kill.
It is a field to watch with interest, though not one yet available for investing in. It is theoretically ingenious but has many hurdles and obstacles before it will ever be ready for use in patients. CRISPR by the way is for clustered regularly interspaced palindromic repeats. Getting the method to where the Cas enzyme, the targeting RNA and the curative DNA can ALL be delivered in a high-yield way to affected cells will take many years to refine and perfect if it can in fact be made workable at all for humans.
Thank you. I really appreciate your time and expertise and I look forward to learning even more in the future.
Thanks DR KSS for comprehensive information about future gene therapy.
Learned a lot ..
Om
Is there any company using CRISPR technology ?
http://editasmedicine.com/
Great, concise and informative as always. It is interesting that there is redundancy in the code so that if one base pair is altered in the DNA it does not necessarily mean the eventual protein will be erroneous.
There seems to be a company working on a similar technology developing so-called “smart bomb” type drugs. If you go over to the “Antibiotics don’t get no respect..” piece by Dr KSS and look up comment 129 and 203, you wil find the answer.