To: Forest Gump who wrote (1748 ) 7/22/1998 10:14:00 AM From: Graham Marshman Read Replies (2) | Respond to of 4028
Forest, the one totally proven scientific fact is that it's a waste of your time answering Graystone. He's an auto-skip. Anyway, the following long posts are reposted from a couple of PMs between me and a trial member. He claims expertise and offers his opinion on the science. Graham ---------- To: Christian Leon From: Graham Marshman Wednesday, Jul 22 1998 9:55AM EST Christian, Yes I'll be glad to post your views. However, I would like you to consider one thing before I do. If you read the CYGS website, you will see that the process discussed for telomeres is that the vector will splice in the single strand DNA during the mitosis period. There would be no time when it was lying around in the cell unattached. You have defined very well the current state of technology which, to my mind, is also a good statement of CYGS value with the new work they have discussed. I know that the details given are limited, however I'd be interested in your thoughts. Also Mike Skillern at CYGS has expressed a willingness to discuss the technology with any callers. Taking it this extra step would be of considerable value. Graham ----------------------------- To: Graham Marshman From: Christian Leon (Trial Member) Wednesday, Jul 22 1998 9:36AM ET Hi...I wanted to make a few comments to people on the CYGS board but there seems to be a restriction that keeps new members from posting. I was wondering if I pass this along if you could post it from me. A perspective from a biomedical molecular biologist. I tried to get Jane J. Jackson to do it, but I think she got suspended for posting above the 20/6 hour limit. Haven't seen a post from her in a while...thanks if you can do this. My comments are below. Hi...I have a few thoughts on CYGS that I would like to share but there seems to be a restriction on new members for posting to the board. I was wondering if I pass this along if you could post this for me.....thanks. I think it is great when companies can come out with new drug delivery technology to circumvent curent problems in this area, but I think that the technology from CYGS is preliminary at best and highly speculative. This is my view as a Biomedical Molecular Biologist who is familiar with many aspects of the field. The idea of gene therapy technology has been around for years and there are many companies and university research labs working on this but work has been slow because of many difficulties. The problem is not in the method of delivery as several methods have been developed such as retroviral delivery, gene gun, etc. The problem is what happens to the DNA after it has been placed into the body. Dna tends to have a short half life meaning it does not stay around for long. It tends to degrade over a period of several hours. Someone mentioned this in a post and they are correct. Cells have a miraculaous way of cleaning things up inside them. Short strands of DNA are identified as not being part of the genome and thus are not kept stable. This is especially true for single stranded DNA, which is even more unstable since it has nothing to pair to, and even more so for RNA which is made from DNA and is used to actually make the protiens or "drugs". Thus the effectiveness of simply placing DNA into the body is questionable. Repeated delivery is almost necessary unless you can get integration into the genome somehow which also has a problem because integration could occur in DNA that codes for another important protien the cell already uses causing its disruption. Another problem is dosage. How much DNA do you use? And how much of this actually survives the delivery process? How much of this actually encodes for protien and how much protien does it make. This is probably the biggest problem in gene therapy. A drug is only good if you can deliver enough to do the job but not too much so cause side effects. Companies like Merck etc., spend years working on this alone for regular pill drugs and even then, it's not perfect. A drug will act differently depending on one's particular genetic makeup, metabolism rate, etc. Usually an optimal narrow window is defined which will result in the least amount of side effects and the most help. Strict guidelines must be met before a drug passes clinical testing and is marketed. This aspect of gene therapy is difficult to control. Another problem is target delivery. How do you specify where you want a piece of DNA to go? This specificty is very broad. Adenoviruses can be usd to deliver drugs to non-dividing cells such as brain cells, but the rest of the body has cells that are always dividing. Viruses can possibly be constructed to attack certain kinds of cells but even this is random. Suppose you wanted a virus to attack skin cells to deliver DNA there only. OK.....but you cannot control which skin cells get the virus. If you inject 1 billion viruses they are not going to attack 1 billion different cells. Some cells will not be attacked, others will be attacked more than once, a lot of virus may be destroyed by the bodies immune system as well before it even gets to do anything. A cell that gets multiple DNA strands delivered will theoretically make more of the protien drug than one that gets attacked once. Again we get into the dosage problem. Also, what if skin cells around the left arm get attacked more than on the right leg. Virus distribution around the body is completely random once injected and cannot be controlled. Obviously this will not do any good either. I don't hold any CYGS stock and do not recommend a buy or a sell. I just wanted to inform investers of some things about this technology they should know to make a better judgement of what they want to do. Like I said, a new DNA drug delivery system is great but would be completely useless if what happens next still cannot be controlled. Even so, based on determining dosage, target delivery, etc., it would be years of testing before such a new method would be standard in medicine and the company could profit from this.