The following is a collection of resources that will be fascinating to those interested in what is happening within the work of using adeno-associated viruses (AAV) to develop drugs that manipulate genes for desirable clinical outcomes. The resources listed below are grouped as follows: Introduction, AAV Manufacturing & Production  and Compliance & Regulatory Considerations.

Introduction – Adeno-Associated Virus (AAV)

Article: Oligonucleotides: Opportunities, Pipeline and Challenges

1970s, nearly a half century later, only three oligonucleotide drugs have been approved by the FDA. However, the field is gaining momentum and the clinical benefits of the more than 135 oligonucleotide therapeutics currently in various stages of clinical trials are extremely promising.

Video: Engineering Adeno-Associated Viruses for Gene Therapy

Video: Adeno-Associated Virus (AAV) – An Introduction

Video: Making Adeno Associated Virus (AAV)



Manufacturing & Production – Adeno-Associated Virus (AAV)

Video: Production and Titering of Recombinant Adeno-Associated Viral Vectors

Article: Production and Titering of Recombinant Adeno-Associated Viral Vectors

In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies in animals, and are also currently being tested in human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family and inherently replicationdeficient.

Article: Large-Scale Recombinant Adeno-Associated Virus Production

Since recombinant adeno-associated virus (rAAV) was first described as a potential mammalian cell transducing system, frequent reports purportedly solving the problems of scalable production have appeared. Yet few of these processes have enabled the development of robust and economical rAAV production. Two production platforms have emerged that have gained broad support for producing both research and clinical grade vectors.

Article: Co-packaging of Multiple Adeno-Associated Viral Vectors in a Single Production Step

Limiting factors in large pre-clinical and clinical studies utilizing adeno-associated virus (AAV) for gene therapy are focused on the restrictive packaging capacity, the overall yields, and the versatility of the production methods for single AAV vector production. Furthermore, applications where multiple vectors are needed to provide long expression cassettes, whether because of long cDNA sequences or the need of different regulatory elements, require that each vector be packaged and characterized separately, directly affecting labor and cost associated with such manufacturing strategies.

Article: Cross-Packaging of a Single Adeno-Associated Virus (AAV) Type 2 Vector Genome into Multiple AAV Serotypes Enables Transduction with Broad Specificity

The serotypes of adeno-associated virus (AAV) have the potential to become important resources for clinical gene therapy. In an effort to compare the role of serotype-specific virion shells on vector transduction, we cloned each of the serotype capsid coding domains into a common vector backbone containing AAV type 2 replication genes. This strategy allowed the packaging of AAV2 inverted terminal repeat vectors into each serotype-specific virions.

Sample Protocol: A Protocol for AAV Vector Production and Purification

The protocol describe at below is typical of methods that are used to propagate and purify AAV vectors for experiments both in vitro and in vivo.

Article: Transient Transfection Methods for Clinical Adeno-Associated Viral Vector Production

Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for purity, potency, and safety required for human parenteral administration. Several methods have been developed to generate recombinant AAV in cell culture, each offering distinct advantages. Transient transfection-based methods for vector production are reviewed here, with a focus on specific considerations for development of AAV vectors as clinical products.

Article: Manufacturing of Recombinant Adeno-Associated Viral Vectors: New Technologies Are Welcome

Recombinant adeno-associated viral vectors (rAAV) are probably the most powerful tools for in vivo gene delivery. Encouraging preclinical data have been followed by successful gene therapy clinical trials including Leber’s congenital amaurosis type 2, hemophilia B,and recently choroideremia. These results together with the market authorization of Glybera, an AAV-based product for the treatment of lipoprotein lipase deficiency,  has prompted skeptical investors and biotechnology and pharmaceuticals companies to move into this field.

Compliance & Regulatory – Adeno-Associated Virus (AAV)

U.S. Pharmacopeia: Manufacturing of Gene Therapy Products

Guidance for Industry: Gene Therapy Clinical Trials – Observing Subjects for Delayed Adverse Events

Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)

FDA Grants Breakthrough Status to Gene Therapy for First Time

Rare Disease Advocacy Groups Receiving FDA Orphan Designations