animalkgb

Alnylam and RNAi: The Truth Hurts

I understand and completely agree with the statements about the pharma industry and the emotional drivers that force many of them to follow in a similiar direction, but the views on siRNA technology itself are simply incorrect.

First monoclonal antibodies are certainly not a fad. They are an incredibly powerful, targeted approach to treatment. the problem was that not much was known about how to produce them reliably and in a consistent formulation. siRNA has a much higher specificity and potency and is much easier to produce. These short RNAs are actually reusable when they are inside cells. The bodies own proteins use these guiding molecules to breakdown mRNA, the precurser to protein, and thus stop the specific biological process (a bit of an oversimplification). The key is that these molecules can be "re-used" and therefore can be used in much smaller amounts, minimizing adverse effects and allowing for higher "relative" dosing while actually using less material. This is essentially the opposite for antisense molecules, which need to be in a high enough ratio in the cells to outcompete the production of mRNA and find its place before a ribozome can make protein.

There is no problem getting these molecules into cells. The problem is getting them to the right cells in the body before our immune cells grab them. That is why Alnylam has chosen their targets wisely. RSV infects the lungs...the most accessible layer of the lungs. The liver is also another viable target in that lipids are sent there relatively intact...so basically they are covering the siRNA molecules with oil. Cholesterol is produced in the liver...

i will admit that the problem with the lungs may be a delivery method...one would likely require an inhaler (which has shown some problems with other types of medicines; though I don't know anything about it), and the liver drug has been injected...which is not very appealing to a patient who can take a small statin every day. Though making a daily pill coated in oil is not a big deal...I take one every day. THey injected a monkey once and reduced cholesterol levels lasted for a month.

getting these molecules in cells is the least of their worries. I have even heard of collision transfection where the sheer force of combination can get nucleic acid into cells. Imagine that...your doctor throws your drug at you once a day!