Article
Biochemistry & Molecular Biology
Sherif G. Ahmed, Casey A. Maguire, Shiliang Alice Cao, Gary J. Brenner
Summary: Schwannomas are tumors derived from Schwann-lineage cells. Currently, treatment options for schwannomas are limited and associated with significant complications. Researchers have successfully reduced tumor volume and pain in experimental models using gene therapy. The safety and efficacy data support the translation of this gene therapy strategy to clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ying Kai Chan, Sean K. Wang, Colin J. Chu, David A. Copland, Alexander J. Letizia, Helena Costa Verdera, Jessica J. Chiang, Meher Sethi, May K. Wang, William J. Neidermyer, Yingleong Chan, Elaine T. Lim, Amanda R. Graveline, Melinda Sanchez, Ryan F. Boyd, Thomas S. Vihtelic, Rolando Gian Carlo O. Inciong, Jared M. Slain, Priscilla J. Alphonse, Yunlu Xue, Lindsey R. Robinson-McCarthy, Jenny M. Tam, Maha H. Jabbar, Bhubanananda Sahu, Janelle F. Adeniran, Manish Muhuri, Phillip W. L. Tai, Jun Xie, Tyler B. Krause, Andyna Vernet, Matthew Pezone, Ru Xiao, Tina Liu, Wei Wang, Henry J. Kaplan, Guangping Gao, Andrew D. Dick, Federico Mingozzi, Maureen A. McCall, Constance L. Cepko, George M. Church
Summary: The study engineered AAV vectors by incorporating short DNA oligonucleotides to antagonize TLR9 activation, reducing innate immune responses and enhancing gene expression in clinically relevant animal models. The engineered vectors can avoid adverse reactions in some models, demonstrating a potential wider therapeutic window for AAV therapies.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, General & Internal
Dezhuang Ye, Jinyun Yuan, Yaoheng Yang, Yimei Yue, Zhongtao Hu, Siaka Fadera, Hong Chen
Summary: This study investigates the potential of focused ultrasound-mediated intranasal delivery (FUSIN) in delivering adeno-associated viral (AAV) vectors to the brain. The results show that FUSIN achieves safe and efficient delivery to spatially targeted brain locations and is comparable to established delivery methods.
Article
Biotechnology & Applied Microbiology
Sandeep R. P. Kumar, Dongsheng Duan, Roland W. W. Herzog
Summary: Muscle-directed gene therapy using AAV vectors is promising for treating neuromuscular disorders. However, there are concerns about immune responses against the vector or transgene products. This review discusses clinical observations and future prospects for addressing these issues through vector engineering and immune modulation.
HUMAN GENE THERAPY
(2023)
Review
Biotechnology & Applied Microbiology
Helena Costa-Verdera, Carmen Unzu, Erika Valeri, Sahil Adriouch, Gloria Gonzalez Aseguinolaza, Federico Mingozzi, Anna Kajaste-Rudnitski
Summary: As the clinical experience in AAV vector-based gene therapies grows, there is a need to better understand and control the host immune responses. Our current understanding of the immune responses to AAV gene therapies is limited, which is further hindered by the lack of replication of clinical findings in preclinical animal models.
HUMAN GENE THERAPY
(2023)
Review
Ophthalmology
Kirsten Bucher, Eduardo Rodriguez-Bocanegra, Daniyar Dauletbekov, M. Dominik Fischer
Summary: Recombinant adeno-associated virus (AAV) is a leading vector for gene therapy in the retina, efficiently transducing retinal cells but also causing intraocular inflammation and immune responses. The eye, being an immune-privileged site, may mitigate these responses, but further research is needed to understand influencing factors.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ah Young Kim, Felix Michael Duerr, Jennifer Phillips, Richard Jude Samulski, Josh C. Grieger, Laurie R. Goodrich
Summary: A formal screening of self-complementary adeno-associated virus (scAAV) vector serotypes in canine joint tissues has not been performed to date. This study aims to identify the most optimal scAAV vector serotype that maximizes transduction efficiencies in canine cell cultures and tissue explant cultures. The results show that scAAV2 and 2.5 have the highest transduction efficiencies among the serotypes, and a dose-response relationship is observed. Further evaluation of the safety and efficacy of scAAV2.5 vector with an appropriate therapeutic gene in vivo is recommended.
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)
Review
Biotechnology & Applied Microbiology
Sha Sha, Andrew J. Maloney, Georgios Katsikis, Tam N. T. Nguyen, Caleb Neufeld, Jacqueline Wolfrum, Paul W. Barone, Stacy L. Springs, Scott R. Manalis, Anthony J. Sinskey, Richard D. Braatz
Summary: The article focuses on analyzing the bottlenecks in rAAV production during cell culture, comparing differences between wild-type and recombinant systems, and proposing future directions for improvement.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Microbiology
Edward E. Large, Michael S. Chapman
Summary: Adeno-associated viruses (AAV) are widely used for gene therapy, and monoclonal antibodies against various AAV serotypes have been developed. Previous studies suggested that neutralizing antibodies inhibit binding to glycan receptors or interfere with post-entry steps. However, recent research has identified a protein receptor and revealed that antibody interference with protein receptor binding may be the predominant mechanism of neutralization.
FRONTIERS IN MICROBIOLOGY
(2023)
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
Biochemistry & Molecular Biology
Giulia Massaro, Amy F. Geard, Wenfei Liu, Oliver Coombe-Tennant, Simon N. Waddington, Julien Baruteau, Paul Gissen, Ahad A. Rahim
Summary: This study provides a comprehensive overview of the current state of gene therapy in lysosomal diseases, including viral gene delivery vectors, relevant pre-clinical studies, and ongoing clinical trials in recent years.
Article
Chemistry, Multidisciplinary
Amelie Bauer, Matteo Puglisi, Dennis Nagl, Joel A. Schick, Thomas Werner, Andreas Klingl, Jihad El Andari, Veit Hornung, Horst Kessler, Magdalena Goetz, Dirk Grimm, Ruth Brack-Werner
Summary: Astrocytes play crucial roles in the central nervous system and are involved in various CNS diseases. This study focuses on astrocyte-centered diseases and the need for effective and well-characterized gene transfer vectors. The findings highlight the use of a synthetic peptide-displaying AAV9 variant, rAAV9P1, which was shown to efficiently target and transduce human astrocytes. The study also identifies the specific receptors and intracellular pathways utilized by rAAV9P1 for astrocyte targeting. These results enhance our understanding of synthetic AAV vectors for astrocytes and their potential applications in research and medicine.
Article
Medicine, Research & Experimental
Yuqiu Wang, Chen Yang, Hanyang Hu, Chen Chen, Mengdi Yan, Feixiang Ling, Kathy Cheng Wang, Xintao Wang, Zhe Deng, Xinyue Zhou, Feixu Zhang, Sen Lin, Zengmin Du, Kai Zhao, Xiao Xiao
Summary: This study reports a novel AAV serotype, AAVzk2, which exhibits strong liver transduction and liver-specific gene delivery, similar to AAV8 and AAV9, with low immunoreactivity like AAV5. This provides a new therapeutic option for individuals who cannot be treated with AAV8 and AAV9.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)