Article
Multidisciplinary Sciences
Zachary C. Elmore, L. Patrick Havlik, Daniel K. Oh, Leif Anderson, George Daaboul, Garth W. Devlin, Heather A. Vincent, Aravind Asokan
Summary: The membrane-associated accessory protein (MAAP) is identified as a novel viral egress factor that promotes the secretion of AAV serotypes. MAAP contains a cationic amphipathic domain critical for AAV secretion. Restoring MAAP expression can rescue the secretion defect in various AAV serotypes with mutated start sites.
NATURE COMMUNICATIONS
(2021)
Review
Clinical Neurology
Robert Duba-Kiss, Yosuke Niibori, David R. Hampson
Summary: This Mini Review discusses the use of various gene regulatory elements for targeting GABAergic neurons, with a focus on adeno-associated viral vectors, the most widely used class of viral vectors for treating brain diseases.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemical Research Methods
Aurelien Jacob, Laurie Brun, Paloma Jimenez Gil, Lucie Menard, Mohammed Bouzelha, Frederic Broucque, Aline Roblin, Luk H. Vandenberghe, Oumeya Adjali, Cecile Robin, Achille Francois, Veronique Blouin, Magalie Penaud-Budloo, Eduard Ayuso
Summary: Manufacturing viral vectors for gene delivery is challenging, with a scalable baculovirus-insect cell platform being used for producing rAAV vectors. A faster and safer method based on homologous recombination (HR) has been investigated to avoid technical constraints and safety concerns associated with the Tn7 transposition method. The HR system offers increased stability and avoids undesirable bacterial genes, ensuring the generation of safer rAAV biotherapeutic products.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Medicine, Research & Experimental
Kelsey R. Pflepsen, Cristina D. Peterson, Kelley F. Kitto, Maureen S. Riedl, R. Scott McIvor, George L. Wilcox, Lucy Vulchanova, Carolyn A. Fairbanks
Summary: The distribution and kinetics of AAV5 vector following lumbar intrathecal injection in mice were evaluated in this study. Results showed rapid distribution of AAV5 particles to all levels of the spinal cord and dorsal root ganglia, with preferential targeting of DRG tissue and possible clearance mechanisms via DRG macrophages.
MOLECULAR PHARMACEUTICS
(2021)
Article
Engineering, Chemical
Abhiram Arunkumar, Nripen Singh
Summary: This study quantitatively investigated the ultrafiltration behavior of AAVs using different membrane molecular weight cut-off and operating conditions, showing that these factors can impact the flux and transmission of AAV. The study found that a 100 kDa ultrafiltration membrane can act as a completely retentive membrane or as significantly permeable to AAV serotypes depending on the operating conditions.
JOURNAL OF MEMBRANE SCIENCE
(2021)
Article
Clinical Neurology
Amanda L. Gross, Heather L. Gray-Edwards, Cassie N. Bebout, Nathan L. Ta, Kayly Nielsen, Brandon L. Brunson, Kalajan R. Lopez Mercado, Devin E. Osterhoudt, Ana Rita Batista, Stacy Maitland, Thomas N. Seyfried, Miguel Sena-Esteves, Douglas R. Martin
Summary: Researchers have found that intravenous administration of AAV9 vector can effectively treat GM1 gangliosidosis, increasing the lifespan of animals and improving their quality of life and neurological function. After treatment, neurological abnormalities were mild, CSF biomarkers were normalized, and urinary glycosaminoglycans decreased to normal levels.
Review
Biotechnology & Applied Microbiology
Andrew D. Tustian, Hanne Bak
Summary: There is a growing interest in gene therapy products, particularly those utilizing AAV particles. Using a quality by design approach in production can enhance product quality and may become a regulatory expectation. Controlling product attributes and setting predefined goals is crucial in proactive process development through QbD methods.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Review
Chemistry, Multidisciplinary
Hanna J. Wagner, Wilfried Weber, Martin Fussenegger
Summary: The recent approvals and ongoing clinical trials have established adeno-associated virus (AAV) as the leading gene delivery vehicle in gene therapy. Pharmaceutical companies are investing in AAV to expand therapeutic options. The emerging field of synthetic-biologically engineered AAV vectors has great potential to shape future gene therapeutic approaches.
Article
Biochemistry & Molecular Biology
Melad Farraha, Renuka Rao, Sindhu Igoor, Thi Y. L. Le, Michael A. Barry, Christopher Davey, Cindy Kok, James J. H. Chong, Eddy Kizana
Summary: This study aimed to develop a biological alternative to electronic pacemakers by using gene therapy to convert cardiomyocytes into sinoatrial node-like cells. The results showed that the transduction of hTBX18 gene resulted in morphological, molecular, physiological, and functional changes in the cardiomyocytes, recapitulating the pacemaker phenotype. The use of a clinically relevant vector opens new prospects for the development of biological pacemakers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Gregg A. Duncan
Summary: One of the key challenges in gene therapy is to overcome pre-existing and therapy-induced immune responses, as well as to enhance the distribution and activity of AAV in target tissues. Interdisciplinary approaches may help overcome these obstacles and create new opportunities for precision gene therapy.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Chemistry, Medicinal
Zachary J. Tickner, Michael Farzan
Summary: Riboswitches offer advantages for regulating AAV-delivered gene therapy due to their small genomic footprints and non-immunogenicity. Their ligand-sensing aptamer domains can be exchanged for diverse regulation. Recent screening methods allow rapid isolation of high-performing riboswitches.
Article
Medicine, Research & Experimental
Peng Zou
Summary: This study compared the performance of two allometric scaling approaches and a body-weight-based dose conversion approach for dose prediction in gene therapy. The body-weight-based approach underestimated the dose in some vectors, while the allometric scaling approach overestimated the dose. The allometric scaling between log GEF and W-0.25 was appropriate in certain conditions.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Kimitoshi Takeda, Masanori Noda, Takahiro Maruno, Susumu Uchiyama
Summary: Mass photometry (MP) is a label-free, single-molecule technique that can determine molecular mass distribution with low sample consumption and short time. The strict optical settings are crucial for accurate estimation of high-molecular mass samples. This study emphasizes the critical calibration of the mass photometer and presents a method for optimizing instrument settings.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Virology
Shonisani Wendy Limani, Njabulo Mnyandu, Abdullah Ely, Reubina Wadee, Anna Kramvis, Patrick Arbuthnot, Mohube Betty Maepa
Summary: The study demonstrated the use of recombinant adeno-associated viruses (AAVs) to model the replication of different hepatitis B virus (HBV) subgenotypes, showcasing the efficacy of the AAV8-A1 murine model for anti-HBV drug development.
Article
Multidisciplinary Sciences
Kirsten Bucher, Eduardo Rodriguez-Bocanegra, Bernd Wissinger, Torsten Strasser, Simon J. Clark, Andreas L. Birkenfeld, Dorothea Siegel-Axel, M. Dominik Fischer
Summary: AAV vectors produced in different host cells have different immunogenic properties due to the differences in residual host cell components and post-translational modifications. The inflammatory cytokine responses induced by AAV vectors were lot-specific rather than production platform-specific or manufacturer-specific. These responses could be reduced by blocking toll-like receptor 9 signaling or enzymatically reducing DNA using DNase.
SCIENTIFIC REPORTS
(2023)