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Michael Fulks MDNov 16, 2023 11:17:00 AM2 min read

siRNAs- The latest and greatest treatment approach for a wide variety of conditions

Dr. Michael Fulks, Consulting Medical Director, highlights two recent studies showing the range of conditions potentially treatable by a single subQ shot of a small interfering RNA (siRNA).

Two recent articles in NEJM and a short topic review in JAMA show the range of conditions potentially treatable by a single subQ shot of a small interfering RNA (siRNA) every 6 months or so. And, unlike lots of genetic and biologic Rx including many monoclonal antibodies, this stuff is easy and inexpensive to make. siRNAs are very short segments of double-stranded RNA that will target a particular complimentary messenger RNA for degradation preventing production of a target protein. These strands can be delivered to the organ of interest (such as liver) via viral and non-viral complexes by subQ injection and appear to function for at least 6 months, usually with minimal side effects. Once appropriate targeting for an organ like the liver is developed, then it is simple to target any mRNA in hepatic cells essentially turning off the activity (transcription) of those genes.

Initially, siRNA studies mostly focused on rare single gene diseases to reduce production of an abnormal protein or remove a block to the production of an under-produced protein. More recently, interest has shifted to include common (and potentially more profitable) conditions such as hyperlipidemia and hypertension where targeting the production of a single protein can still be important in control.

The first article from NEJM in 2020 covers a trial of the siRNA drug inclisiran for patients with or at high risk for atherosclerotic CV disease already receiving maximal doses of statins. They received the drug on day 1, day 90 and then q6 months. A 50% additional reduction in LDL levels was achieved without more side effects than the placebo arm.

The second article from NEJM in 2023 covers zilebesiran, an siRNA drug that targets angiotensin production. A single dose was administered subQ to hypertensive patients with 24 weeks of follow up resulting in sustained systolic BP reduction of >10 mm Hg without other side effects including any hypotension.

siRNAs have the potential to favorably impact many conditions with high convenience and low risk of side effects once delivery systems targeted to specific organs are fine-tuned. They also have the potential to eventually become low cost as they are simple to make unlike many biologics.


About the Author

Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. More recently, Mike has consulted for CRL participating in its mortality research on laboratory test results, BP and build, and in the development of risk-scoring tools for laboratory and non-laboratory data.