A Better Way Series, Part I: The Gene Therapy Delivery Problem
Jonathan Thon, Ph.D. • February 14, 2023
Gene therapy is conceptually simple: diseases that are caused by harmful genetic variants can be treated or even cured by editing the DNA of the affected cells. Advances in genomics and gene editing have already overcome challenges related to identifying and repairing the relevant genes. Bottlenecks remain however, including the ability to translate our wins in very specific, small population and expensive use cases to more prevalent disease and broader use cases.
The ‘last’ hurdle keeping gene therapy from becoming a viable therapeutic option is the ability to target delivery of editing technology to the right cells in the body. We can do better
The gene therapies that have reached the clinic to date work by extracting the patient’s blood or other affected tissue, isolating relevant cells, editing their DNA in a lab, and depleting the patient’s immune system before transplanting the edited cells back into the body. This is a risky procedure that requires specialized training and facilities, and involves a lengthy hospital stay.
Patients deserve better.
At STRM.BIO our mission is to democratize gene therapy by using a simpler, safer, practical delivery technology, bringing cures for genetic diseases to life. In this series of blog posts I’ll outline how current gene therapy delivery methods fall short, and explain why the STRM.BIO team sees microvesicles as the key to overcoming gene therapy’s most critical hurdle.
It is critical to the future of the field that we find a way to deliver gene therapies into the target cells of patients in vivo—that is, by injecting therapies in a standard clinical setting, without the need for hospitalization, immunosuppression, or specialist medical training and facilities.
The following criteria need to be met:
Capacity: the newest high-precision, multi-target gene editing constructs are larger than their predecessors and will need larger delivery vehicles.
Targeting: treatments for different diseases need to edit genes in different types of cells; their delivery vehicles must therefore have the corresponding cell-type specificity (cell tropism). Precision cell tropism means lower doses and fewer side-effects from off-target delivery.
Safety: delivery vehicles must be well tolerated by patients.
Dose repeatability: some gene therapy applications will require more than one dose.
This is a complex challenge. Many potential solutions to the delivery problem have emerged during the 30 year history of gene therapy, each with unique advantages and disadvantages. In the next post, we’ll outline the history of gene therapy delivery vectors and introduce you to the diverse technologies that are being developed today.