Retinal gene therapy advancing into clinical reality

 

Take-home message: Gene therapy can provide transformative disease-modifying effects, with potentially lifelong clinical benefits after a single therapeutic administration. The most advanced retinal gene therapy program in the United States is in phase III study.

 

 

By Jeffrey D. Chulay, MD, Special to Ophthalmology Times

Alachua, FL-Genes encode proteins that perform an array of functions. Many diseases have a genetic aspect whereby a mutated gene is passed down from generation to generation. Mutated genes may encode abnormal proteins or disable the production of a protein completely, either of which can cause disease.

Gene therapy introduces a functional copy of the gene into a patient’s own cells. By correcting the underlying genetic defect that causes disease, gene therapy can potentially provide lifelong clinical benefits after a single administration.

Adeno-associated viruses

Gene therapy uses viral vectors to deliver genes into cells affected by disease. Viral vectors have been optimized for this purpose by removing pathogenic elements and severely impairinghttp://www.modernmedicine.com/tag/retinitis-pigmentosa the viruses’ ability to replicate.

Adeno-associated virus (AAV) vectors are well suited for treating retinal diseases. AAV is a small, simple, non-enveloped virus with only two native genes, making the virus straightforward to work with from a vector-engineering standpoint. AAV vectors can carry gene sequences up to 4,000 base pairs in length.¹

More than 90% of human genes have coding sequences less than 3,000 base pairs in length.

In case you missed it: Reducing IOL prediction error

AAV vectors have been used in more than 100 human clinical trials with no serious adverse events traced to the use of AAV as the gene delivery vector and are considered to be the safest viral vector for use in human gene therapy. AAV has never been linked to human disease and elicits only a mild immune response. AAV vectors have no viral genes remaining, virtually eliminating the possibility that any viral genes will cause an adverse event.¹

AAV vectors can now be produced at a commercial scale in compliance with current Good Manufacturing Practice for use in clinical trials and future marketed products. As many as 2.4 x 10¹⁴ vector copies per liter have been produced, with batches up to 100 liters, using the latest advances in large-scale viral vector production technology.²

Studies have confirmed that the purification process eliminates all but a trace amount of the raw materials used during manufacture, in many cases below assay detection levels.³

Internal server error