A new class of drug called siRNA, a cousin of mRNA, can enter cells and stop a specific gene from producing a harmful protein. This enables highly targeted treatments, such as new drugs that reduce a type of cholesterol by over 95% with a single, long-lasting injection.

After decades of work, small interfering RNA (siRNA) has overcome delivery challenges to become a mature, "de-risked" platform, primarily for liver-directed targets. This now enables powerful medicines like a once-yearly injection for high cholesterol, representing a major public health breakthrough.

To overcome the historical issue of oncolytic viruses being sequestered by the liver, Accession re-engineers a human virus so it cannot infect any human cells. Only after this safety step is it re-targeted to infect only cancer cells, ensuring precise delivery and avoiding systemic side effects.

Instead of using CRISPR for gene editing (cut and replace), Seek Labs harnesses its natural function. Their platform programs CRISPR to find and 'chop up' viral DNA and RNA, directly lowering the viral load and allowing the host's immune system to take over.

Recludix posits that for chronic diseases, inhibiting a protein's specific function is superior to complete degradation. Degrading a protein can disrupt its other essential roles (e.g., mitochondrial function), leading to unnecessary toxicity. Inhibition offers a more targeted, reversible approach with a potentially better long-term safety profile.

The commercial advantage of one-time CRISPR/Cas9 therapies is shrinking. Advancements in RNA modalities like siRNA now offer durable, long-lasting effects with a potentially safer profile. This creates a challenging risk-reward calculation for permanent gene edits in diseases where both technologies are applicable, especially as investor sentiment sours on CRISPR's long-term safety.

Gene editing pioneer David Liu is developing a platform that could treat multiple, unrelated genetic diseases with a single therapeutic. By editing tRNAs to overcome common nonsense mutations, one therapy could address a wide range of conditions, dramatically increasing scalability and reducing costs.

While focused on oncology, Yosemite's portfolio company Tune Therapeutics is using epigenetic editing to develop a functional cure for Hepatitis B. This is a strategic cancer play, as chronic Hepatitis B is the leading global cause of liver cancer.

Voyager CEO Al Sandrock explains their AAV capsids are engineered to be so potent at crossing the blood-brain barrier that doses can be an order of magnitude lower than standard. Crucially, the capsids are also designed to *avoid* the liver, directly addressing the toxicity issues that have plagued the field.