Gene therapy for inborn error of immunity - current status and future perspectives

Development of hematopoietic stem cell (HSC) gene therapy (GT) for inborn errors of immunity (IEIs) continues to progress rapidly. Although more patients are being treated with HSC GT based on viral vector mediated gene addition, gene editing techniques provide a promising new approach, in which transgene expression remains under the control of endogenous regulatory elements.

Many gene therapy clinical trials are being conducted and evidence showing that HSC GT through viral vector mediated gene addition is a successful and safe curative treatment option for various IEIs is accumulating. Gene editing techniques for gene correction are, on the other hand, not in clinical use yet, despite rapid developments during the past decade. Current studies are focussing on improving rates of targeted integration, while preserving the primitive HSC population, which is essential for future clinical translation.

As HSC GT is becoming available for more diseases, novel developments should focus on improving availability while reducing costs of the treatment. Continued follow up of treated patients is essential for providing information about long-term safety and efficacy. Editing techniques have great potential but need to be improved further before the translation to clinical studies can happen.