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
Cell Biology
Jinliang Li, Shannon C. Kelly, Jan R. Ivey, Pamela K. Thorne, Kelly P. Yamada, Tadao Aikawa, Renata Mazurek, James R. Turk, Kleiton Augusto Santos Silva, Amira R. Amin, Darla L. Tharp, Christina M. Mueller, Hrishikesh Thakur, Emily Leary, Timothy L. Domeier, R. Scott Rector, Kenneth Fish, Federico Cividini, Kiyotake Ishikawa, Craig A. Emter, Michael S. Kapiloff
Summary: This study assessed the biodistribution of self-complementary serotype 9 adeno-associated virus (AAV9sc) biologics in swine, demonstrating successful targeted delivery of cardiomyocyte-selective viral vectors without toxic effects. The results indicate the potential efficacy of these vectors in preclinical experimental settings.
PHYSIOLOGICAL GENOMICS
(2022)
Review
Clinical Neurology
Katarzyna Kotulska, Aviva Fattal-Valevski, Jana Haberlova
Summary: Spinal muscular atrophy is a neuromuscular disease caused by mutation of the SMN1 gene, but disease modifying therapies have shown effectiveness in improving motor functions of patients with SMA.
FRONTIERS IN NEUROLOGY
(2021)
Article
Gastroenterology & Hepatology
Nadja Meumann, Marti Cabanes-Creus, Moritz Ertelt, Renina Gale Navarro, Julie Lucifora, Qinggong Yuan, Karin Nien-Huber, Ahmed Abdelrahman, Xuan-Khang Vu, Liang Zhang, Ann-Christin Franke, Christian Schmithals, Albrecht Piiper, Annabelle Vogt, Maria Gonzalez-Carmona, Jochen T. Frueh, Evelyn Ullrich, Philip Meuleman, Steven R. Talbot, Margarete Odenthal, Michael Ott, Erhard Seifried, Clara T. Schoeder, Joachim Schwable, Leszek Lisowski, Hildegard Buning
Summary: This article reports two gene vector variants, MLIV.K and MLIV.A, which were obtained through in vivo AAV peptide display selection in mice. They showed improved hepatocyte targeting and transduction efficiency compared to AAV2 and AAV8, and have potential for liver disease treatment.
Article
Engineering, Biomedical
Yizheng Yao, Jun Wang, Yi Liu, Yuan Qu, Kaikai Wang, Yang Zhang, Yuxin Chang, Zhi Yang, Jie Wan, Junfeng Liu, Hiroshi Nakashima, Sean E. Lawler, E. Antonio Chiocca, Choi-Fong Cho, Fengfeng Bei
Summary: Engineered AAV9 variants displaying specific cell-penetrating peptides on the capsid show enhanced transduction of central nervous system cells in small and large animals.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Meera Vyas, Natalie M. Deschenes, Karlaina J. L. Osmon, Zhilin Chen, Imtiaz Ahmad, Shalini Kot, Patrick Thompson, Chris Richmond, Steven J. Gray, Jagdeep S. Walia
Summary: This study assessed the effects of gene therapy in an ABGM2 mouse model and found that it led to a reduction in GM2 accumulation and long-term persistence of vector genomes in the brain and liver.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Fabian Blanc, Alexis-Pierre Bemelmans, Corentin Affortit, Charlene Josephine, Jean-Luc Puel, Michel Mondain, Jing Wang
Summary: Viral-mediated gene therapy shows great potential for the treatment of deafness. Injection into the cisterna magna can achieve efficient binaural transduction without affecting auditory function and cochlear structures.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
John W. Day, Richard S. Finkel, Eugenio Mercuri, Kathryn J. Swoboda, Melissa Menier, Rudolf van Olden, Sitra Tauscher-Wisniewski, Jerry R. Mendell
Summary: This study examined anti-adeno-associated virus serotype 9 antibody titers in patients with spinal muscular atrophy undergoing gene therapy with Onasemnogene abeparvovec. The results suggest that most patients are eligible for treatment, but some individuals may have antibody titers that could affect therapeutic outcomes.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Biotechnology & Applied Microbiology
Benjamin Stolte, Olivia Schreiber-Katz, Rene Guenther, Claudia Diana Wurster, Susanne Petri, Alma Osmanovic, Maren Freigang, Zeljko Uzelac, Markus Leo, Otgonzul von Velsen, Wibke Bayer, Ulf Dittmer, Christoph Kleinschnitz, Tim Hagenacker
Summary: This study investigated the prevalence of anti-AAV9 antibodies in adult patients with SMA and found that only a small percentage of patients had elevated antibody titers. This suggests that gene therapy with AAV9 vectors may be feasible in adult SMA patients.
HUMAN GENE THERAPY
(2022)
Article
Medicine, Research & Experimental
Qinglan Ling, Matthew Rioux, Yuhui Hu, MinJae Lee, Steven J. Gray
Summary: The study showed that the gene replacement therapy with AAV9/hSURF1 significantly improved complex IV activity and content, and effectively alleviated biochemical abnormalities induced by SURF1 deficiency. Additionally, the treatment also mitigated blood lactic acidosis and demonstrated no significant toxicity in animal studies.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Integrative & Complementary Medicine
Yi-lin Xie, Ji-yao Wang, Yun He, Xiao-min Yu, Qing-yun Zheng, Chen Ling, Xi-lin Feng, Li-qing Zhu
Summary: The use of melittin significantly enhances transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors (rAAV2) both in vitro and in vivo. Pre-incubation of rAAV2 vectors with melittin greatly improves their transduction efficiency in HEK293 and Huh7 cells. This research expands the pharmacological potential of melittin and provides a new strategy to enhance gene therapy using rAAV vectors.
JOURNAL OF INTEGRATIVE MEDICINE-JIM
(2023)
Article
Multidisciplinary Sciences
Amedee Mollard, Cecile Peccate, Anne Forand, Julie Chassagne, Laura Julien, Pierre Meunier, Zoheir Guesmia, Thibaut Marais, Marc Bitoun, France Pietri-Rouxel, Sofia Benkhelifa-Ziyyat, Stephanie Lorain
Summary: The study focused on the impact of the necrosis-regeneration process on the efficiency of AAV therapy, finding that regenerated muscles showed reduced transgene expression, which may limit the application of AAV-based therapies.
SCIENTIFIC REPORTS
(2022)
Article
Agriculture, Dairy & Animal Science
Savannah R. Gregg, Madison R. Barshick, Sally E. Johnson
Summary: The study found that injection of hyaluronic acid can have anti-inflammatory effects without disrupting the normal muscle repair process after exercise.
Article
Medicine, Research & Experimental
Yuan Meng, Dong Sun, Yiyan Qin, Xiaoyi Dong, Guangzuo Luo, Ying Liu
Summary: This study demonstrated that cell-penetrating peptides (CPPs) can enhance the transduction efficiency of AAV9, a promising vector for CNS diseases treatment, by facilitating its ability to cross the blood-brain barrier (BBB) and induce higher expression of target genes in the brain.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Cell Biology
Kissaou T. Tchedre, Subrata Batabyal, Melissa Galicia, Darryl Narcisse, Sourajit Mitra Mustafi, Ananta Ayyagari, Sai Chavala, Samarendra K. Mohanty
Summary: The study demonstrates that intravitreal injection of rAAV2-based MCO-I for retinal gene therapy is safe, with no detectable inflammatory or immune reaction in the dog retina. The virus vector is cleared via urine and faeces, with no presence of transgene in faeces after 3 weeks post-injection.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Xiufang Pan, Yongping Yue, Maria Boftsi, Lakmini P. Wasala, Ngoc Tam Tran, Keqing Zhang, David J. Pintel, Phillip W. L. Tai, Dongsheng Duan
Summary: The study found that complete elimination of CpG motifs in the ITR does not impact the biological activity of the AAV vector. CpG-free ITRs could be valuable in engineering therapeutic AAV vectors.
Article
Veterinary Sciences
Sarah M. Schneider, Garett T. Sansom, Lee-Jae Guo, Shinji Furuya, Brad R. Weeks, Joe N. Kornegay
Summary: This study systematically assessed cardiac lesions in carrier dogs, GRMD dogs, and normal dogs, and found that quantitative analysis of the cross-sectional area of fibrosis can distinguish the health status of different groups of dogs. The features identified in GRMD dogs are compatible with those of DMD, validating GRMD as an effective model for studying cardiomyopathy.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Letter
Cardiac & Cardiovascular Systems
Dongsheng Duan, Kevin M. Flanigan, Annemieke Aartsma-Rus
Article
Biochemistry & Molecular Biology
Samayitree Das, Sharon D'Souza, Bhavya Gorimanipalli, Rohit Shetty, Arkasubhra Ghosh, Vrushali Deshpande
Summary: Infection mediated ocular surface stress responses are important early defense mechanisms in response to host cell damage. Understanding the etiology and pathogenesis of ocular infections is crucial for early diagnosis and effective treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Krishnatej Nishtala, Trailokyanath Panigrahi, Rohit Shetty, Dhanananajay Kumar, Pooja Khamar, Rajiv R. Mohan, Vrushali Deshpande, Arkasubhra Ghosh
Summary: This study used quantitative proteomics to identify key factors involved in the differentiation-dependent protein profile changes in human corneal stromal cells. The differentiated fibroblasts and myofibroblasts expressed proteins related to cellular signaling pathways, SLIT-ROBO pathways, and extracellular matrix, indicating their potential role in corneal wound healing. The identified proteins such as profilin 1 and talin could potentially serve as targets for treating corneal fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Sharon D'Souza, Rohit Shetty, Archana Padmanabhan Nair, Ruchika Agrawal, Mor M. Dickman, Pooja Khamar, Rudy M. M. A. Nuijts, Arkasubhra Ghosh, Swaminathan Sethu
Summary: Ocular surface conditions like dry eye disease can cause severe discomfort and pain. It is difficult to determine the cause and prescribe the right treatment in patients with a lot of discordance between symptoms and signs. By stratifying and evaluating corneal structural features and tear molecular factors in patients with ocular surface pain, clinicians can improve diagnosis and treatment choice.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Vishnu Suresh Babu, Ashwin Mallipatna, Deepak Sa, Gagan Dudeja, Ramaraj Kannan, Rohit Shetty, Archana Padmanabhan Nair, Seetharamanjaneyulu Gundimeda, Shyam S. Chaurasia, Navin Kumar Verma, Rajamani Lakshminarayanan, Stephane Heymans, Veluchamy A. Barathi, Nilanjan Guha, Arkasubhra Ghosh
Summary: This study reveals unique functional associations between genes and metabolites in retinoblastoma (Rb) tumors. The gene expression patterns and metabolic processes differ between clinically advanced and non-advanced Rb, indicating altered tumor-specific metabolism. Rb tumors have reduced reliance on glycolytic pathways and are regulated by Rb1 and HK1.
Article
Biochemistry & Molecular Biology
Sharon D'Souza, Tanuja Vaidya, Archana Padmanabhan Nair, Rohit Shetty, Nimisha Rajiv Kumar, Anadi Bisht, Trailokyanath Panigrahi, S. J. Tejal, Pooja Khamar, Mor M. Dickman, Ruchika Agrawal, Sanjay Mahajan, Sneha Sengupta, Rudy M. M. A. Nuijts, Swaminathan Sethu, Arkasubhra Ghosh
Summary: Prolonged daily face mask wearing can affect the health of the ocular surface, leading to discomfort and dry-eye-like symptoms. This study found that there were changes in clinical parameters, tear soluble factors, and immune cell proportions in ophthalmologists who wore masks continuously for several months. These changes were distinct from dry eye disease or other common ocular surface conditions.
Letter
Cardiac & Cardiovascular Systems
Janine Ebner, Xiufang Pan, Yongping Yue, Spyridon Sideromenos, Jessica Marksteiner, Xaver Koenig, Karlheinz Hilber, Dongsheng Duan
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Lakmini P. Wasala, Thais B. Watkins, Nalinda B. Wasala, Matthew J. Burke, Yongping Yue, Yi Lai, Gang Yao, Dongsheng Duan
Summary: Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by dystrophin deficiency. In this study, it was found that mu Dys with both H1 and H4 effectively localized to the muscle membrane, restored the dystrophin-associated protein complex, and improved muscle force. On the other hand, mu Dys with only H1 or without H4 did not have the same effects. Therefore, H4 is essential for mu Dys function and H1 facilitates force production. These findings will contribute to the development of next-generation mu Dys gene therapy.
HUMAN GENE THERAPY
(2023)
Article
Oncology
Vishnu Suresh Babu, Anadi Bisht, Ashwin Mallipatna, S. A. Deepak, Gagan Dudeja, Ramaraj Kannan, Rohit Shetty, Nilanjan Guha, Stephane Heymans, Arkasubhra Ghosh
Summary: Our study identifies differentially expressed microRNAs in retinoblastoma and pediatric retina as well as advanced and non-advanced tumors. We provide evidence of the epithelial-mesenchymal transition (EMT) and chemoresistance programs in advanced tumors, potentially related to miR-181a-5p. Our findings highlight the importance of understanding the EMT and chemoresistance mechanisms in tumor progression and suggest miR-181a-5p as a potential therapeutic target.
Article
Cell Biology
Vishnu Suresh Babu, Gagan Dudeja, Deepak Sa, Anadi Bisht, Rohit Shetty, Stephane Heymans, Nilanjan Guha, Arkasubhra Ghosh
Summary: Loss of RB1 and HK1 in retinoblastoma reprograms tumor metabolism, enhancing fatty acid oxidation and mitochondrial ATP production instead of glycolysis dependence. These metabolic perturbations could be potential therapeutic targets for retinoblastoma.
Article
Biotechnology & Applied Microbiology
Nalinda B. Wasala, Yongping Yue, Bryan Hu, Jin-Hong Shin, Gang Yao, Dongsheng Duan
Summary: In this study, the researchers injected the AAV mu Dys vector into mdx mice and observed significant improvements in muscle strength, exercise capacity, and cardiac function. The results suggest that AAV mu Dys therapy has the potential to provide lifelong benefits in patients with Duchenne muscular dystrophy.
HUMAN GENE THERAPY
(2023)
Review
Cell Biology
Subhradeep Sarkar, Priyalakshmi Panikker, Sharon D'Souza, Rohit Shetty, Rajiv R. R. Mohan, Arkasubhra Ghosh
Summary: Corneal transplantation has been a remarkable advancement in medical treatments for corneal diseases. However, it has its own challenges such as graft rejection and shortage of donor corneas. Gene therapy is a promising intervention to mitigate these challenges and help reduce blindness caused by corneal defects and diseases. This review focuses on the recent advances in corneal regeneration using gene therapy and discusses the challenges and potential of gene therapy for corneal diseases.
Review
Biotechnology & Applied Microbiology
Dongsheng Duan
Summary: This mini-review summarizes clinical findings of lethal immunotoxicity induced by high-dose systemic AAV gene therapy and calls for collaborative efforts to better understand the underlying mechanisms and develop effective prevention/treatment strategies.