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Gene Therapy

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...

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Development challenges associated with rAAV-based gene therapies.

Michael W Bolt¹, Joseph T Brady¹, Lawrence O Whiteley¹

¹Pfizer Inc., Drug Safety Research and Development, Cambridge, MA, USA.

The Journal of Toxicological Sciences

|February 4, 2021

Summary

This summary is machine-generated.

Gene therapies offer novel treatments but face challenges with adeno-associated virus delivery. Evolving regulatory demands and potential toxicities like immunogenicity and tumorgenicity require careful nonclinical study.

Keywords:

AAV gene therapy Development challenges Nonclinical toxicity

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Published on: July 14, 2023

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Area of Science:

Biotechnology
Genetics
Pharmacology

Background:

Gene therapies are increasingly developed for treating diseases.
Adeno-associated viruses (AAVs) are common vectors but present manufacturing and clinical challenges.
Regulatory expectations for gene therapy are evolving.

Purpose of the Study:

To discuss the challenges associated with adeno-associated virus (AAV)-based gene therapies.
To highlight nonclinical toxicities observed with rAAV-based gene therapies.
To examine evolving regulatory expectations for gene therapy development.

Main Methods:

Review of current literature on gene therapy development and AAV vector technology.
Analysis of reported nonclinical toxicities associated with rAAV administration.
Discussion of regulatory agency guidelines and requirements for gene therapy trials.

Main Results:

Common toxicities include immunogenicity, hepatotoxicity, and neurotoxicity.
Potential risks such as insertional mutagenesis and tumorgenicity are associated with AAV gene therapies.
Regulatory agencies increasingly request specific nonclinical studies to support clinical trials.

Conclusions:

Manufacturing, nonclinical, and clinical challenges exist for AAV-based gene therapies.
Understanding and mitigating toxicities like immunogenicity and tumorgenicity are critical.
Adapting nonclinical strategies to meet evolving regulatory expectations is essential for advancing gene therapy.