We're now past the initial period of CRISPR investment that was driven almost entirely by proof-of-concept excitement. The first regulatory approvals happened. Some of the early clinical results were genuinely transformative for individual patients. The field was validated. And then the hard work began — figuring out which indications, which delivery approaches, and which company structures are actually investable at scale.
Our partner Dr. Sarah Chen spent eight years at the Broad Institute before joining Basil Health, and her perspective on the CRISPR landscape is more grounded than most of what gets written about it. This piece summarizes where we think the investment opportunities are and — just as importantly — where we're cautious despite the scientific excitement.
What the first generation of CRISPR therapies taught us
The first approved CRISPR-based therapies targeted monogenic blood disorders — conditions where a single gene edit can have a profound clinical effect, and where the target tissue (hematopoietic stem cells) can be edited ex vivo and reinfused. This was the optimal case: clear genetic target, accessible tissue, a definitive clinical endpoint, and patient populations with high unmet need.
The price points — approaching $3M per patient — immediately raised access questions that remain unresolved. The therapies work. The delivery economics are not yet figured out, and the path to broad payor coverage for a $3M one-time treatment requires outcomes-based contracting structures that insurance systems weren't designed for and aren't ready to administer at scale. This is a business model problem as much as a clinical problem.
What we took away from the first generation: the science can work, but the commercialization path is more complex than most of the pitch decks we see acknowledge. CRISPR companies that are serious investment candidates at our stage have to have thought through delivery, manufacturing, and access strategy — not just mechanism validation.
Where we're actively interested right now
Base editing and prime editing represent a meaningful evolution from first-generation CRISPR. These approaches introduce targeted single-nucleotide changes without creating double-strand DNA breaks, which reduces the off-target risk profile and opens up indications where traditional CRISPR was too imprecise. The liver is the primary accessible in vivo target through lipid nanoparticle delivery, and there are genuinely important metabolic and cardiovascular indications within reach via liver-targeted approaches.
In vivo delivery beyond the liver remains a significant technical constraint. The CNS, lung, and muscle are high-priority targets for which LNP delivery doesn't work well, and viral vectors have payload limitations and manufacturing challenges. We're watching AAV capsid engineering and non-viral delivery innovations closely. The companies that solve in vivo delivery to non-liver tissues will have an enormous head start on a large set of indications.
CRISPR in oncology — specifically cell therapy engineering — is moving faster than the in vivo therapeutic programs. Allogeneic CAR-T programs that use CRISPR to knock out rejection-causing HLA proteins and insert tumor-targeting constructs have shown meaningful clinical signals. The manufacturing cost advantage over autologous cell therapy, if it holds at scale, is transformative for the economics of cell-based oncology.
Where we're cautious
Common disease applications — cardiovascular, metabolic, neurological conditions with complex polygenic architecture — are scientifically fascinating and commercially enormous, but the development timeline and risk profile are very different from rare monogenic diseases. A company targeting Alzheimer's with a CRISPR approach is operating on a 15-20 year timeline with massive capital requirements and a highly uncertain clinical path. That may be the right bet for a large crossover fund; it's not the right bet for a $280M Series A fund.
We're also cautious about companies built entirely around a single gene target with no demonstrated delivery innovation or platform breadth. The target exclusivity argument — "we have IP on editing this gene" — doesn't hold if the delivery problem isn't solved, or if the indication is crowded with competing approaches (small molecules, RNA therapies, monoclonal antibodies) that don't require ex vivo manipulation or expensive manufacturing.
The question for any CRISPR investment isn't "does the edit work?" It's "can you make it, get it in, and get it paid for?" Three separate problems. Most companies have answered the first and are still working on the other two.
What we're looking for specifically
The CRISPR companies we'd back at Basil Health share a few characteristics that separate them from the broader field:
- A delivery platform that represents a genuine technical advance, not just application of existing LNP or AAV approaches to a new indication
- A first indication with a clear regulatory path, a patient population with measurable unmet need, and a biomarker endpoint that can read out within 12-18 months of dosing
- A manufacturing strategy that's thought through — ideally a CDMO partnership with defined tech transfer milestones, or an internal manufacturing capability that's already been demonstrated at clinical scale
- A team that includes someone who has actually moved a cell or gene therapy through CMC review with FDA, not just someone who's studied it
The science in CRISPR is extraordinary, and we believe it will generate transformative medicines over the next decade. Our job is to be specific about which companies have the right pieces in place to navigate from brilliant science to approved treatment. That's a narrower set than the number of companies actively raising money in this space.
