How CRISPR-Edited Donor Islet Cells Are Opening a Path Toward a Functional Cure for Type 1 Diabetes

Speaking to BioPharm International®, Steve Harr, MD, president and CEO of Sana Biotechnology, discusses clinical findings from UP421, the company's gene-modified islet cell therapy candidate for type 1 diabetes (T1D), and the broader implications of the result for the cell therapy field.

UP421 is derived from pancreatic islet cells obtained from a recently deceased donor. Sana Biotechnology used clustered regularly interspaced short palindromic repeats (CRISPR) gene editing to knock out 2 genes and knock in 2 genes before transplanting the modified cells into the muscle of a T1D patient, Dr Harr explains. At 14 months post-transplant, the patient continued to produce insulin without immunosuppression, an outcome Harr describes as particularly significant given the complexity of the immune challenge involved.

What does Sana Biotechnology's UP421 result mean for the future of allogeneic cell therapy?

Dr Harr notes that the patient presented a dual immune barrier: standard allogeneic rejection from receiving donor cells, compounded by a pre-existing immune response to islet cells resulting from T1D itself. The therapy overcame both, he emphasizes.

The company’s scientists had initially projected that surviving 28 days post-transplant would indicate durable immune evasion, a hypothesis the 14-month data have now supported, Dr Harr points out. "I think it gives a lot of people a lot of hope that we are at a period where we can realistically believe that there is a cure on the horizon for type 1 diabetes," he says.

Dr Harr positions the result within a broader evolution of CRISPR gene editing, in which the technology has gone from a primary therapeutic modality targeting rare monogenic disorders to a precise enabling tool within complex, broadly applicable cell therapy programs. He identifies 4 scientific disciplines that must advance in parallel to fully realize the therapeutic potential of this approach: stem cell biology, CRISPR gene editing, transplant immunology, and manufacturing sciences.

View insight into Sana Biotechnology’s hypoimmune technology here.

About the speaker

Steve Harr, MD, President and CEO, Sana Biotechnology

Prior to co-founding Sana, Dr Harr served as chief financial officer and head of Corporate Development for Juno Therapeutics until its acquisition by Celgene in early 2018. He was a member of the board of directors of Loxo Oncology prior to its acquisition by Eli Lilly and Company in early 2019. Dr Harr also was a co-founder and member of the board of directors of JW Therapeutics, a cell therapy company in China. Prior to joining Juno, Dr Harr was at Morgan Stanley, as managing director and head of Biotechnology Investment Banking, and previously as a biotech research analyst and co-head of global healthcare research. He obtained his MD from Johns Hopkins University School of Medicine. He was an internal medicine resident at the University of California, San Francisco, and performed research at Harvard Medical School and Massachusetts General Hospital.