A new strategy to enhance gene therapy for sickle cell disease microbiologystudy

Researchers described a promising new approach for using gene therapy to treat sickle cell disease in the journal Human Gene Therapy. To improve the efficacy of gene therapy when using anti-sickling beta globin gene transfer, they added cyclosporin (CsH) to increase transduction by inhibiting lentiviral restriction factors.

Anne Galy, Ph.D., from Inserm, and co-authors, applied a novel lentivirus-based gene therapy strategy in CD34⁺ hematopoietic progenitor and stem cells (HSPCs) obtained from cord blood. They first demonstrated that the addition of CsH enhanced transgene expression levels in CD34⁺ cells, which remained viable and functional after being treated.

Next, they transduced CD34⁺ cells obtained from the cord blood of newborns with sickle cell disease. The cells were transduced with a lentiviral vector delivering the gene encoding the anti-sickling beta globin HbAS3 protein. The investigators showed that lentiviral transduction was enhanced by CsH and led to therapeutic levels of expression of HbAs3.

“In addition to its ability to enhance the efficiency of transduction, CsH has previously been reported to preserve cell viability,” stated the investigators. “Our data confirmed published studies showing that HSPCs treated with CsH appear to retain normal hematopoietic differentiation potential.”

“This is an exciting advancement for both ex vivo gene therapy in general and for improving treatment for patients with sickle cell disease specifically,” says Managing Editor of Human Gene Therapy Thomas Gallagher, Ph.D., from the University of Massachusetts Chan Medical School.