Article
Biotechnology & Applied Microbiology
Neel Mehta, Renald Gilbert, Parminder S. Chahal, Maria J. Moreno, Nasha Nassoury, Nathalie Coulombe, Viktoria Lytvyn, Mario Mercier, Dorothy Fatehi, Wendy Lin, Emily M. Harvey, Lin-Hua Zhang, Nazila Nazemi-Moghaddam, Seyyed Mehdy Elahi, Colin J. D. Ross, Danica B. Stanimirovic, Michael R. Hayden
Summary: This study aimed to develop a more efficacious AAV gene therapy vector for the treatment of LPLD. The researchers identified AAV8 pVR59 as a superior vector compared to AAV1 (Glybera), with significantly better therapeutic effects at lower doses. AAV8 pVR59 treatment led to long-term correction of LPLD and improvement in pathology.
HUMAN GENE THERAPY
(2023)
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
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
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
Lyubava Belova, Alexander Lavrov, Svetlana Smirnikhina
Summary: Cellular 3D structures, such as organoids, are important for biomedical research. However, there are challenges in delivering transgenes to these structures. This review explores ways to improve the efficiency of transgene delivery.
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
Medical Laboratory Technology
Junji Kobayashi, Takuya Minamizuka, Masaya Koshizaka, Yoshiro Maezawa, Hiraku Ono, Koutaro Yokote
Summary: The study found that serum HDL-C is an extremely useful marker for discriminating LPL deficiency from SHTG in the Japanese population, with high sensitivity and specificity, which can serve as an important indicator of the type of disease in patients.
CLINICA CHIMICA ACTA
(2021)
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)
Article
Cell Biology
Burcak Ozes, Lingying Tong, Morgan Myers, Kyle Moss, Alicia Ridgley, Zarife Sahenk
Summary: This study demonstrated that NT-3 gene transfer therapy can improve muscle function and physiology in aged mice, restoring muscle size and oxidative state. It has important implications for managing age-related sarcopenia.
Article
Medicine, Research & Experimental
Andrew D. Marques, Michael Kummer, Oleksandr Kondratov, Arunava Banerjee, Oleksandr Moskalenko, Sergei Zolotukhin
Summary: Machine learning (ML) is used to train algorithms on data from adeno-associated virus (AAV) capsid libraries to predict the assembly of unknown capsid variants into viable virus-like structures. By utilizing artificial neural networks (ANNs) and support vector machines (SVMs), significant mutation patterns in AAV2-derived capsids, such as N495, G546, and I554, are identified. The study demonstrates the predictive power of ML in vector design through the creation and validation of comparative libraries.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Mika Ito, Naomi Takino, Takamasa Nomura, Akihiko Kan, Shin-ichi Muramatsu
Summary: Modifying the AAV3 viral capsid by introducing three substitutions on the surface loop reduced its reactivity with pre-existing antibodies, leading to enhanced transduction efficiency in human hepatocytes. This engineered AAV3 variant, AAV.GT5, showed significantly higher transduction efficiency in hepatocytes compared to AAV8 vectors, making it a promising candidate for future liver-targeted gene therapy clinical trials.
SCIENTIFIC REPORTS
(2021)
Review
Neurosciences
Tao Wang, Xun Zhu, Hyun Yi, Jun Gu, Shue Liu, Sari Izenwasser, Vance P. Lemmon, Sabita Roy, Shuanglin Hao
Summary: Opioid use disorder (OUD) is a disease of the CNS with diverse manifestations. Current pharmacotherapy for OUD is limited by side effects, leading to a need for non-pharmacological approaches. Viral vector mediated gene therapy offers a potential new avenue for treating OUD.
EXPERIMENTAL NEUROLOGY
(2021)
