Developing guidelines for AAV gene treatments

Developing guidelines for AAV gene treatments

Horizon scanning at the MHRA results in the acquisition of external financing, enabling our scientists to engage in new area of standardization that will assist the developers and producers of AAV gene treatments.

The Issue

Gene therapies are drugs that modify an individual’s genes in order to prevent, treat, or cure disease. 
These novel techniques belong to the category of medications known as Advanced Therapy Medicinal Products or ATMPs (other ATMP are cell therapies). 
gene therapy drug consists of carrier or vector that facilitates the transfer of genetic material or genes into cells. 
Gene treatments based on Adeno-associated viral (AAV) vectors, which are non-replicating, non-pathogenic, single-stranded DNA parvoviruses, are currently field of innovation and expansion. 
Nonetheless, this field may face analytical and manufacturing obstacles.
Analytical methods to assess the presence of impurities, quality, and concentration of product have been developed, but they are performed without common point of reference, and different analytic techniques measure different characteristics of the product, limiting comparisons between products, batches, and sites of manufacture. 
Standardization of AAV products would enable manufacturers to harmonise dosing and the quality of their goods, thereby boosting patient confidence in these therapies and enhancing the safety of these potentially life-changing revolutionary drugs.

The necessary modification

Horizon scanning in this instance revealed need for standardisation of AAV products to support developers and manufacturers of these therapies, to enable patients to access these novel products, and to guarantee they are suitably regulated and safe and effective. 
Without benchmarking material, it is difficult to establish the concentration (copies or particles per mL) and empty/full particle ratio of their products. 
To this goal, accessible and universally applicable AAV reference resources are required to improve the field.

What the MHRA did

To assist with this matter, we combed the life sciences funding ecosystem for suitable funding opportunities to facilitate the production and characterization of an AAV reference material. Together with colleagues at the UK Cell and Gene Therapy Catapult (CGTC), we won money from the Department of Business, Energy, and Industrial Strategy’s (BEIS) Regulators’ Pioneer Fund (RPF) to support the 6-month research.

Using its new state-of-the-art bioreactors and facilities at Braintree, the CGTC generated and purified a batch of AAV2 material, which was then analyzed by Enzyme-Linked Immunosorbent Assays (ELISA), electron microscopy, and Polymerase Chain Reaction (PCR). We experimented with freeze-drying the material, which eliminates the need for a cold-chain supply chain, so facilitating future distribution. Multiple external collaborators, ranging from industrial stakeholders to university laboratories, are currently assessing the materials’ “fitness for use” as a reference material.


Through horizon scanning, we identified the need for AAV reference materials to support the future standardisation of AAV-based gene therapies, which will increase patient confidence in these therapies and the safety of these innovative medicines. By securing external grant funding, we are getting closer to achieving our goal of AVV standardisation. 
Through this initiative, we have also established strong collaborative working relationships with the CGTC and network of AAV standards experts.
Scientist Sarah Kempster, who led the work for the MHRA, stated, “Obtaining funding from the Regulators Pioneers Fund was crucial to making this project reality; it has allowed us to build network of experts in the field, ensuring that the MHRA is at the forefront of new technologies in gene therapy analytics, leading to improved patient health.”

 Electron micrograph of AAV viral particles

This study was made possible by grant from the Department of Business, Energy, and Industrial Strategy’s £3.7 million Regulators’ Pioneer Fund (BEIS). 
The fund enables UK regulators and local authorities to contribute to the creation of regulatory environment that unleashes creativity and makes the United Kingdom the finest place to start and grow business. 
The Cell and Gene Therapy Catapult is member of the Catapult Network, which assists businesses in developing innovative products and services. 
Innovate UK built this network of world-leading technology and innovation facilities.
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