Developing the first WHO International Standard for lentiviral-based gene therapy 

NIBSC are developing the first WHO International Standard for lentiviral vectors, as reported in a recent publication in Human Gene Therapy Methods.

The scientists hope that the standard, which they expect to produce within two years, will ensure the safety and quality of future lentiviral-based gene therapy products.

Assuring safety and quality

Lentiviral vectors (LVs) provide a method of delivering new genetic material into a target cell. They hold great potential for gene therapy applications, already being used for immunodeficiency disorders and chimeric antigen receptor (CAR) T-cell cancer immunotherapies, and with further products being investigated in over 70 clinical trials worldwide.

Although LVs are considered safe, uncontrolled insertion of vectors can disrupt nearby genes causing them to become harmful, and in some cases tumorigenic. Currently the most effective way to reduce this risk is by regulating the number of copies that integrate into the hosts’ genetic material. 

In 2016, WHO approved NIBSC’s application to develop a standard for lentiviral products. This standard aims to regulate copy number insertion, improving the safety and quality of LVs used in gene therapy applications.  

About the standard

The first WHO lentiviral standard will comprise a panel of three standards, made using genomic DNA from Human HEK293T cells without LV integration, with a single copy of LV integrated and with five copies of LV integrated.

These standards will primarily be used for the validation of internal in-house standards used in different laboratories.

This work will build on NIBSC’s expertise in developing over 1,000 International Standards over the past 40 years, including 11 genomic reference materials for cancer diagnostics and genetic testing.

Dr Yuan Zhao, study author and leader of the Gene Therapy section at NIBSC, comments:

"We hope this standard will meet demand from the gene therapy community for materials to support the future control and standardisation of lentivirus-based products.We anticipate it will take around 2 years for this critical tool to be made available for developers of gene therapies."

Dr Christian Schneider, Director of NIBSC added:

 "This WHO IS will be important for three milestone stages of lentiviral product development; the establishment of the manufacturing process, the determination of clinical dose and patient safety follow-up."