In Vivo Genome Editing of Stem Cells Induced by LNP-Based Delivery of mRNA

Part of the job as a pediatric hematologist for Michael P. Triebwasser, MD, PhD, is to take care of patients during their bone marrow transplantation. Just last week, he took care of a patient with a severe combined immunodeficiency (SCID) disorder and another with a bone marrow disorder.

Even though there has been progress in the use of autologous cells for ex vivo gene therapies for hematopoietic disorders like sickle cell disease and beta thalassemia, Triebwasser warns that it still requires the invasive procedure of taking cells out of the body, putting electrophoresis on these cells, and “conditioning” the patients to get rid of their own hematopoietic stem cells (HSCs) to make room for the gene-edited ones. That’s why Triebwasser said that he and others have been on the hunt for “the holy grail of HSC gene therapy”—in vivo genome editing of HSCs.

“In theory, we can replace that gene or correct it in some way and offer them a curative therapy that doesn’t have some of the same issues that hematopoietic stem cell transplantation (HSCT) does, namely graft versus host disease,” Triebwasser...