Gene Correction of Induced Pluripotent Stem Cells Derived from a Murine Model of X-Linked Chronic Granulomatous Disorder

摘要: Gene therapy presents an attractive alternative to allogeneic haematopoietic stem cell transplantation (HSCT) for treating patients suffering from primary immunodeficiency disorder (PID). The conceptual advantage of gene correcting a patient's autologous HSCs lies in minimizing or completely avoiding immunological complications arising while conferring the same benefits immune reconstitution upon long-term engraftment. Clinical trials targeting X-linked chronic granulomatous (X-CGD) have shown promising results this context. However, clinical these been limited by issues poor engraftment gene-transduced cells coupled with transgene silencing and vector induced clonal proliferation. Novel vectors incorporating safety features such as self-inactivating (SIN) mutations long terminal repeats (LTRs) along synthetic promoters driving lineage-restricted sustainable expression gp91phox are expected resolve current pitfalls require rigorous preclinical testing. In chapter, we outlined protocol which X-CGD mouse model derived pluripotent (iPSCs) utilized develop platform investigating efficacy profiles novel prior evaluation.