Cellectis, a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today the publication of a new research paper in Molecular Therapy – Methods & Clinical Development, demonstrating the efficacy of its TALEN-mediated gene correction of mutated PIK3CD gene in APDS1 T-cells.
The research work described in this article was jointly conducted by Imagine Institute and Cellectis teams, the biotech company said.
About APDS1: Activated phosphoinositide 3-kinase δ syndrome (also known as APDS type 1 or APDS1) is a rare but devastating disease caused by gain-of-function mutations in the PIK3CD gene and resulting in a combined immunodeficiency.
Approved treatments for APDS1 consist in prophylactic measures including long term antibiotics and Ig (immunoglobulin) replacement therapy. Allogeneic hematopoietic stem/progenitor cell (HSPC) transplantation has been proposed as a definitive treatment for APDS1. However, the lack of compatible donor as well as graft failure, graft instability, and poor graft function are still major challenges that must be overcome to reach a positive therapeutic outcome. Thus, so far there are neither optimal nor long-term therapeutic solutions for APDS1 patients and new alternative treatments are highly regarded, the company said.
The study published here aims at exploring an alternative therapeutic strategy by correcting the mutated PIK3CD gene associated to APDS1 by gene editing.
This article describes a TALEN®-mediated gene insertion strategy that allows targeted correction of the dominant gain-of-function mutation of the PIK3CD gene by insertion of a functional sequence in a precise manner. Results show efficient gene insertion in APDS1 patients’ T-cells, normalization of PI3K signaling and rescue of T-cell cytotoxic functions.
“This successful demonstration of PIK3CD gene correction warrants the development of a gene therapy approach to treat p110δ dysregulations in a long-term fashion. This proof-of-concept study paves the way for the future development of a bona fide gene surgery candidate to potentially cure APDS1” said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis.