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Adeno-Associated Virus (AAV): Small Virus, Big Impact – Promising Gene Therapy Vectors for the 21st Century and Beyond

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Special Issue Editor

Dr. Kim Van Vliet

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Guest Editor

Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA
Interests: AAV vectors; adeno-associated virus; gene therapy; AAV capsid structure; AAV serotype; AAV; parvovirus; transduction

Special Issue Information

Dear Colleagues,

Advances and improvements in adeno-associated virus (AAV) vector technologies have resulted in rapid expansion of their development for use in the clinic. Successes in clinical trials have demonstrated their effectiveness as a therapeutic gene delivery vehicle for a variety of monogenic disorders, many of which currently lack treatments or therapies. The human immune response presents a challenge in using these vectors for gene delivery and a better understanding of the interaction of the virus capsid with the components of the immune system guides the development of next-generation vectors. Studies focused on the role of the virus capsid and interactions with cellular components will also result in improvements in tissue targeting and transduction efficiency. More efficient tissue targeting and gene expression will result in lower required effective therapeutic doses and will provide safer treatments for patients. This Special Issue will highlight recent advances in AAV vectorology, novel AAV gene therapy vectors, and current progress in moving these vectors into the clinic for a variety of disorders.

This Special Issue of Microorganisms will be dedicated to the following themes: advances in AAV viral vectors for their development as therapeutic gene delivery vehicles for use in the clinic; modified AAV capsids for the purpose of specific tissue targeting, improved production and purification, or immune evasion; development of novel AAV vectors for clinical conditions; investigations of novel AAV serotypes or modified AAVs for use in the clinic; next-generation AAV vectors.

Dr. Kim Van Vliet
Guest Editor

Manuscript Submission Information

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Keywords

AAV vectors
adeno-associated virus (AAV)
gene therapy
AAV capsid structure
parvovirus
AAV serotype
transduction

Published Papers (2 papers)

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Research

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19 pages, 2694 KiB

Open AccessArticle

Monobac System–A Single Baculovirus for the Production of rAAV

by Lionel Galibert, Aurélien Jacob, Adrien Savy, Yohann Dickx, Delphine Bonnin, Christophe Lecomte, Lise Rivollet, Peggy Sanatine, Marjorie Boutin Fontaine, Christine Le Bec and Otto-Wilhelm Merten

Microorganisms 2021, 9(9), 1799; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091799 - 24 Aug 2021

Cited by 8 | Viewed by 3566

Abstract

Large-scale manufacturing of rAAV is a bottleneck for the development of genetic disease treatments. The baculovirus/Sf9 cell system underpins the first rAAV treatment approved by EMA and remains one of the most advanced platforms for rAAV manufacturing. Despite early successes, rAAV is still a complex biomaterial to produce. Efficient production of the recombinant viral vector requires that AAV replicase and capsid genes be co-located with the recombinant AAV genome. Here, we present the Monobac system, a singular, modified baculovirus genome that contains all of these functions. To assess the relative yields between the dual baculovirus and Monobac systems, we prepared each system with a transgene encoding γSGC and evaluated vectors’ potency in vivo. Our results show that rAAV production using the Monobac system not only yields higher titers of rAAV vector but also a lower amount of DNA contamination from baculovirus. Full article

(This article belongs to the Special Issue Adeno-Associated Virus (AAV): Small Virus, Big Impact – Promising Gene Therapy Vectors for the 21st Century and Beyond)

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Review

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22 pages, 1515 KiB

Open AccessReview

A Small Virus to Deliver Small Antibodies: New Targeted Therapies Based on AAV Delivery of Nanobodies

by Noelia Silva-Pilipich, Cristian Smerdou and Lucía Vanrell

Microorganisms 2021, 9(9), 1956; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091956 - 15 Sep 2021

Cited by 9 | Viewed by 4895

Abstract

Nanobodies are camelid-derived single-domain antibodies that present some advantages versus conventional antibodies, such as a smaller size, and higher tissue penetrability, stability, and hydrophilicity. Although nanobodies can be delivered as proteins, in vivo expression from adeno-associated viral (AAV) vectors represents an attractive strategy. This is due to the fact that AAV vectors, that can provide long-term expression of recombinant genes, have shown an excellent safety profile, and can accommodate genes for one or several nanobodies. In fact, several studies showed that AAV vectors can provide sustained nanobody expression both locally or systemically in preclinical models of human diseases. Some of the pathologies addressed with this technology include cancer, neurological, cardiovascular, infectious, and genetic diseases. Depending on the indication, AAV-delivered nanobodies can be expressed extracellularly or inside cells. Intracellular nanobodies or “intrabodies” carry out their function by interacting with cell proteins involved in disease and have also been designed to help elucidate cellular mechanisms by interfering with normal cell processes. Finally, nanobodies can also be used to retarget AAV vectors, when tethered to viral capsid proteins. This review covers applications in which AAV vectors have been used to deliver nanobodies, with a focus on their therapeutic use. Full article

(This article belongs to the Special Issue Adeno-Associated Virus (AAV): Small Virus, Big Impact – Promising Gene Therapy Vectors for the 21st Century and Beyond)

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