RNA Interference as the New Gene Therapy

It's easy to draw parallels between work on RNA interference (RNAi) today and gene therapy circa 1986. Both have demonstrated tremendous potential as platforms for building therapies to treat - or cure - a wide range of conditions that presently lack effective therapies. Both are powerful tools for changing our genes and biochemistry; a comparative lack of understanding can harm the recipients of therapies:

Long-term use of RNA interference (RNAi) can be fatal in mice, scientists report in this week's Nature. However, some short hairpin RNAs (shRNAs) suppressed viral infections without killing the mice, suggesting that the technology may still be useful -- if used carefully.


Irvin Chen at the University of California at Los Angeles, also not a co-author, noted he also has found that some shRNAs directed against CCR5 for HIV-1 therapy proved toxic with long-term use in primary human T-cells and chimeric mice, while other shRNAs were not toxic in the same setting. "The more data we accumulate about what shRNAs and siRNAs are and are not toxic, the better we can get at the mechanisms and in the future hopefully be able to predict toxicity," he said.

Much the same was said about gene therapy in its infancy, and rightfully so. These are some of the most challenging areas of modern biotechnology - but then building powered aircraft that could actually fly was challenging a century ago. The challenges of the present day are the foundations of medicine far more capable than most researchers envisage.

Gene therapy has advanced greatly in the past 20 years - dozens of clinical trials are presently underway or in planning. RNAi medicine will advance more rapidly, as today's enabling biotechnology is (quite literally) a thousand times more capable than that of 1986. Still, the human factor is the eternal sticking point; no matter how powerful your bioinformatics, it still takes much the same time to sort out funding, organize research efforts, fill out paperwork, pay a cut to government wastrels, and so forth.

A central target for RNAi research - and much gene therapy research for that matter - is cancer:

RNAi Versus Cancer:

RNAi is so new only three companies are experimenting with drugs based on it, but none are targeting cancer. Unlike other drugs on the market, SanoGene's experimental drug targets multiple cell origins of brain tumors, blocking the invasion of cells into other tissue. So far, it has shown extremely positive results for the drug in animal models, according to its founders

More RNAi Versus Cancer:

scientists were the first to use what are known as 'small interfering RNAs' to block the spread of human colorectal cancer cells implanted in laboratory mice. ... Over the last couple of years people have talked a lot about cell-culture studies of siRNAs, but only a handful of labs have pushed it to animal models, which we need to do before going on to clinical trials."

Revolution in the fight against cancer & viruses:

"We've exploited this process by creating short interfering RNA, or siRNA, that are being developed into drugs to fight viruses and cancer," he said. "We've now taken this a step further and worked out how we can create siRNA with different cellular properties to target different diseases."


"By 'tweaking' the structure of siRNA to target specific diseases, we can dictate whether we want a particular siRNA-based drug to block or promote an immune response, to increase the effectiveness of the treatment," he said. "While our research is at an early stage, human trials using siRNA are currently underway in the USA and Europe. We're confident our have a significant impact on the way siRNA is being developed as a weapon in the fight against viruses and cancer," said Professor Williams.

Medical revolutions tend to be slow-burning affairs of a decade or more - but RNAi will be the next gene therapy, I'll wager. Ten years from now, there will be dozens of trials, just as for gene therapy in the present day. Like gene therapy, RNAi is a powerful technology with great application to many age-related conditions - and ultimately to making adaptive alterations to human biochemistry to better withstand or repair the cellular damage at the root of aging.

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