Scientists at universities and pharmaceutical companies alike in the next several years may be working in a transformed research environment, one in which ideas may more quickly and cheaply be translated into effective therapies to treat a wide array of life-robbing illnesses.
Instead of targeting offending proteins in disease with small-molecule drugs -- the standard way to develop new pharmaceuticals today -- the hope is to interfere with a different type of molecule, already famous in some guises, called a nucleic acid.
Through the Human Genome Project launched two decades ago, scientists produced a Rosetta stone for getting a handle on all our deoxyribonucleic acid, or DNA. DNA is the stuff of genes, of course. Genes encode and direct the production of proteins, which in turn give us form and enable us to function.
Using this key for what a healthy human's genes ought to look like, researchers now have made huge strides in figuring out which genetic abnormalities play important roles in disease.
In cancer, for instance, the DNA mutations that drive out-of-control tumor growth typically are those that cause genes to be switched on abnormally. This leads to abnormal biochemical signaling by proteins. Many of these proteins now are targets for new drug development by major pharmaceutical companies.
But DNA is not the only nucleic acid of interest. Another type of nucleic acid, called RNA, promises to put academic scientists on the cutting edge of drug development. It's these research scientists at universities who are most likely to make the groundbreaking discoveries that lead to whole new classes of drugs. Yet even lab scientists who work at major academic medical centers -- alongside physician-colleagues who lead clinical trials -- have traditionally found it prohibitively time-consuming and expensive to translate their discoveries into useful therapies.RNA Interference
Fortunately, that situation now may be changing, thanks to the Nobel Prize-winning discovery of RNA interference. RNA interference is a process whereby small RNA molecules govern the activity of specific genes. There is a class of molecules called short inhibitory RNAs, or siRNAs, which can be made in the laboratory and "tuned" to interfere with and inactivate almost any gene. Researchers already can reliably accomplish this in the lab. Soon, it may also prove possible to inhibit disease-causing genes in humans.
The same UCSF researchers who took the early lead in developing biotechnologies that now are widely used to track genes and genetic abnormalities in disease - including expression profiling, fluorescence in situ hybridization (FISH) and comparative genomic hybridization - now have formed a new, multi-university consortium. They have reached out to other exceptionally talented scientists at several leading cancer research centers to advance cancer drug development based on siRNA.
The siRNA therapeutics consortium includes laboratory and clinical researchers from UCSF, UC Berkeley, UC San Diego and MD Anderson Cancer Center, and is led by Joe Gray, PhD
, and Frank McCormick, PhD
, at UCSF and Steve Martin, PhD, at UC Berkeley. The consortium includes experts in cancer target identification, experts in basic siRNA research and experts in drug delivery.
Read more at Jeffrey Norris, UCSF Science Cafe