Researchers mention in vivo CRISPR therapies

A thread circulating on X this week pointed to a real shift in the CRISPR conversation: attention is moving from approved ex vivo treatments toward earlier-stage in vivo programs aimed at rare diseases and, in some cases, sickle cell. The post referenced preclinical work, meetings on construct design and delivery, and a new U.S. regulatory discussion around individualized therapies. Those references match what researchers and regulators have been discussing in public forums in 2026. The distinction matters because the first approved CRISPR medicines, including Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy for sickle cell disease and transfusion-dependent beta thalassemia, rely on editing cells outside the body and then reinfusing them. In vivo editing refers to delivering the editing machinery directly into the patient, with the goal of changing cells where they are. That approach has been a research target for years, but most programs remain early and technically difficult. ### Why are people suddenly talking about in vivo CRISPR instead of the approved sickle-cell model? Casgevy established that CRISPR-based medicine could clear regulators, but it did so with an ex vivo process that requires stem-cell collection, chemotherapy conditioning and specialized treatment centers. That has left researchers looking for ways to make gene editing simpler to deliver and potentially usable in more diseases, including disorders that do not lend themselves to bone-marrow harvest and transplant-style procedures. The X thread’s references to rare disease and sickle cell fit that broader push. Public 2026 reviews from the Innovative Genomics Institute say in vivo editors are being pursued for liver targets and inherited disorders, while meeting programs this spring have highlighted tissue-specific delivery, durability and translational development as central hurdles. ### What did the 2026 workshops actually focus on? (crisprtx.com) ASGCT’s 2026 workshop listing described a four-hour session on “advancing the next generation of tools for precision gene editing in vivo.” The society said the workshop covered editor engineering, targetability, delivery systems and translational development, with an emphasis on efficient, tissue-specific and durable correction. That language tracks with what scientists mean when they talk about “construct design.” In practice, the design problem is not just the guide RNA or editing enzyme. (innovativegenomics.org) It also includes the delivery vehicle, the tissue target, how long the editor stays active and how developers try to limit off-target editing. ASGCT’s 2026 annual meeting materials show the field has made these tool-building questions a central part of the conference program. (annualmeeting.asgct.org) ### What changed on the regulatory side in 2026? The FDA on February 23, 2026, issued draft guidance on what it calls a “plausible mechanism framework” for individualized therapies targeting specific genetic conditions with a known biological cause. The agency said the framework is meant to help developers generate evidence of safety and effectiveness when randomized trials are not feasible because patient populations are very small. (annualmeeting.asgct.org) The guidance specifically discusses genome editing and RNA-based therapies. FDA said key criteria include identifying the disease-causing abnormality, showing that the therapy addresses the root cause or a proximate biological pathway, relying on natural-history data, and confirming successful target modification or editing. (fda.gov) For researchers working on bespoke or mutation-specific CRISPR approaches, that is the clearest sign yet that regulators are trying to define how individualized editing products might be reviewed. The guidance is draft and “not for implementation,” the FDA page says, but it gives developers a public framework to work from. (fda.gov) ### Where does the ethics debate come in? Gene-drive examples, including proposals involving ticks, sit outside the mainstream therapeutic pathway but often appear in the same public discussions because they use related editing concepts and raise broader questions about control, reversibility and ecological spillovers. The X thread’s use of gene-drive talks as an ethical example reflects that overlap in debate, even though human in vivo therapies and environmental gene drives are regulated and evaluated very differently. (fda.gov) The immediate next public source for this story is ASGCT’s on-demand release of 2026 workshop recordings, including the in vivo precision-editing session. On the policy side, the FDA’s February 23, 2026 draft guidance remains open as the main public document for developers working on individualized genome-editing therapies.