Autologous Transplantation with Genetically Edited Cells: Pitfalls and Possibilities

Two developments in stem cell culture and genetic editing have to leadto high hopes of successful options for gene therapy. Creating inducedpluripotent stem cells (iPSC’s) from a patient, followed by CRISPR-Cas9editing of the causative mutation for the disease was theoretical anelegant combination that could lead to gene therapy with autologouscells. The pitfalls, however were not trivial. There were more off-targeteffects of the gene editing than was anticipated and the modified iPSC’swere also potentially dangerous by integration of the genes for alterationof the differentiation potential. Direct transdifferentiation is difficult touse in this context, because the cells need to be expanded after the geneediting and before transdifferentiation. Non-integrative induction maysolve this problem, while the recently developed Base Editor technique, an improvement of the CRISPR/Cas9 technique, may avoid off-targeteffects of the genetic editing.

Keywords:

Induced Pluripotent Stem Cells , Autologous transplantation , Genetically Edited Cells