Interesting proof-of-concept for multiplex base editing in embryos.
That said, we were surprised by the lack of optimization and benchmarking. The study does not explore guide stoichiometry, delivery parameters, RNA stabilization strategies, or next-generation ABE variants designed to improve editing precision and reduce bystander activity.
We were also surprised by the comparison against Cas9 rather than against the current generation of adenine base editors.
Finally, editing outcomes in MII-stage embryos cannot always be inferred from observations in HEK293 or hESC systems, making developmental context an important variable to consider.
At Origin Genomics, we believe these questions are the real frontier. We're building experimental systems to systematically study how editor architecture, delivery, guide design, and developmental context influence editing outcomes in human embryos.
The paper demonstrates feasibility. The more interesting question is how much further efficiency and precision can be pushed with systematic optimization.
Full debate can be found here: youtube.com/watch?v=kQxd397z…
In germline gene correction, risks don’t just affect one person, they can carry forward across generations. But the same is true for benefits. Preventing a serious genetic disease once could mean no one in that family ever has to face it again.
Our founder, @CathyTie, debates Glenn Cohen, Deputy Dean of Harvard Law School at the Annual Daniel Callahan Program hosted by the Hastings Center.