Article
Biotechnology & Applied Microbiology
Adrian Westhaus, Marti Cabanes-Creus, Timo Jonker, Erwan Sallard, Renina Gale Navarro, Erhua Zhu, Grober Baltazar Torres, Scott Lee, Patrick Wilmott, Anai Gonzalez-Cordero, Giorgia Santilli, Adrian J. Thrasher, Ian E. Alexander, Leszek Lisowski
Summary: This study validated a functional transduction (FT)-based method for rapid identification of novel AAV variants. Compared with existing replication-competent (RC) strategies, the mRNA-based FT selection was found to be the most optimal AAV selection method. The study also revealed that the AAV-p40 promoter is a ubiquitously active promoter that can be modified for cell-type-specific expression by incorporating specific binding sites.
HUMAN GENE THERAPY
(2022)
Article
Multidisciplinary Sciences
Petr O. Ilyinskii, Alicia M. Michaud, Christopher J. Roy, Gina L. Rizzo, Stephanie L. Elkins, Teresa Capela, Aparajita C. Chowdhury, Sheldon S. Leung, Takashi K. Kishimoto
Summary: ImmTOR nanoparticles enhance the efficacy of systemic AAV gene therapy by blocking the formation of neutralizing antibodies and promoting hepatic transgene expression. This multi-faceted mechanism makes ImmTOR a promising candidate for improving treatment outcomes and enabling repeat dosing.
Article
Neurosciences
David Goertsen, Nicholas C. Flytzanis, Nick Goeden, Miguel R. Chuapoco, Alexander Cummins, Yijing Chen, Yingying Fan, Qiangge Zhang, Jitendra Sharma, Yangyang Duan, Liping Wang, Guoping Feng, Yu Chen, Nancy Y. Ip, James Pickel, Viviana Gradinaru
Summary: The study developed AAV capsids that achieved robust transgene expression in the brain with decreased liver targeting after non-invasive administration, enabling more targeted systemic gene delivery. This organ-specific targeting extends to marmosets, allowing for non-invasive gene delivery with distinct transgene expression patterns. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates opens up new avenues for basic research and therapeutic possibilities beyond naturally occurring serotypes.
NATURE NEUROSCIENCE
(2022)
Article
Immunology
Manish Muhuri, Wei Zhan, Yukiko Maeda, Jia Li, Anoushka Lotun, Jennifer Chen, Katelyn Sylvia, Ishani Dasgupta, Motahareh Arjomandnejad, Thomas Nixon, Allison M. Keeler, Sangeetha Manokaran, Ran He, Qin Su, Phillip W. L. Tai, Guangping Gao
Summary: The use of miRNA binding sites in rAAV vectors has shown promise in reducing transgene immunity and achieving sustained transgene expression in muscle cells. Combinatorial miR-142BS and miR-652-5pBS have been effective in inhibiting transgene expression in APCs, while maintaining high expression in muscle cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Laura P. van Lieshout, Miranda Rubin, Katrina Costa-Grant, Stacy Ota, Diane Golebiowski, Troy Panico, Eli Wiberg, Klaudia Szymczak, Richard Gilmore, Marissa Stanvick, Brenda Burnham, Jeff Gagnon, Ifeyinwa Iwuchukwu, Guang Yang, Iraj Ghazi, Alex Meola, Ryan Dickerson, Thomas Thiers, Luke Mustich, April Hayes, Israel Rivas, Jason Lotterhand, Nancy Avila, James McGivney, Jin Yin, Tim Kelly
Summary: ""Transient transfection using plasmid DNA is a common method for producing adeno-associated virus (AAV) vectors. A dual-plasmid system, pOXB, has been developed with an alternative sequence arrangement, which results in significantly increased AAV vector productivity and full capsid packaging compared to the traditional triple transfection method. This system has shown reproducibility across different AAV genomes and capsid serotypes, and it is scalable at a bioreactor scale of 50-L. The pOXB dual-plasmid system offers significant process gains while maintaining the flexibility of transient transfection."
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Elena Barbon, Charlotte Kawecki, Solenne Marmier, Aboud Sakkal, Fanny Collaud, Severine Charles, Giuseppe Ronzitti, Caterina Casari, Olivier D. Christophe, Cecile V. Denis, Peter J. Lenting, Federico Mingozzi
Summary: Von Willebrand disease (VWD), the most common inherited bleeding disorder, has limited efficacy with current liver-directed gene therapy. This study developed a gene therapy strategy using an optimized AAV vector and endothelial-targeting peptide to deliver the VWF gene into endothelial cells, achieving long-term expression.
Article
Medicine, Research & Experimental
Alexandra C. Stanton, Kim A. Lagerborg, Liana Tellez, Allison Krunnfusz, Emily M. King, Simon Ye, Isaac H. Solomon, Mohammadsharif Tabebordbar, Pardis C. Sabeti
Summary: In this study, scientists used mRNA-based directed evolution strategy in mice and cynomolgus macaques to identify engineered AAV vectors with increased brain transduction capability and decreased liver tropism. While the macaque-derived variants showed significant improvement in transducing the macaque brain, the mouse-derived variants, both from this study and other groups, were not effective. This study highlights the importance of using appropriate animal models for evaluating novel AAVs intended for CNS delivery.
Article
Engineering, Environmental
Yang Hu, Zhen Zhong, Mengting Lu, Yaseen Muhammad, Syed Jalil Shah, Hui He, Wenxue Gong, Yaofei Ren, Xin Yu, Zhongxing Zhao, Zhenxia Zhao
Summary: This study proposes a novel hybrid MXene/MIL-100(Fe) that generates H2O2 in situ for efficient degradation of organic contaminants through photo-Fenton catalysis. The results show that MXene/MIL-100(Fe) has higher H2O2 generation and degradation rates, and significantly outperforms other photo-Fenton catalysts in terms of thiacloprid degradation.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Jung Ah Choi, Kunyu Wu, Gyoung Nyoun Kim, Nasrin Saeedian, Seung Han Seon, Gayoung Park, Dae-Im Jung, Hoe Won Jeong, Na Hyung Kim, Sang Hwan Seo, Sangkyun Lee, Manki Song, C. Yong Kang
Summary: The study utilized a dual serotype recombinant VSV vaccine strategy to develop a ZIKV vaccine, with challenge studies conducted in a mouse model showing robust immune responses induced by the vaccine.
JOURNAL OF GENERAL VIROLOGY
(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.
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)
Article
Pharmacology & Pharmacy
Vishnu Suresh Babu, Atish Kizhakeyil, Gagan Dudeja, Shyam S. Chaurasia, Veluchami Amutha Barathi, Stephane Heymans, Navin Kumar Verma, Rajamani Lakshminarayanan, Arkasubhra Ghosh
Summary: Host defense peptides, namely hyper-charged wholly cationic antimicrobial dodecapeptides (CAPs), demonstrated excellent bactericidal activities against pathogenic bacteria and exhibited potent anticancer properties against retinoblastoma cells. Two CAPs, HC3 and HC5, were found to induce apoptosis in retinoblastoma cells and showed synergistic effects when combined with the chemotherapeutic drug topotecan.
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.
