Article
Immunology
Corinne J. J. Smith, Nikki Ross, Ali Kamal, Kevin Y. Kim, Elizabeth Kropf, Pascal Deschatelets, Cedric Francois, William J. Quinn, Inderpal Singh, Anna Majowicz, Federico Mingozzi, Klaudia Kuranda
Summary: AAV gene transfer shows promise in treating genetic diseases, but the host immune response poses challenges. This study characterizes the innate immune response to AAV in human whole blood, finding that high levels of neutralizing antibodies can increase inflammation and vector uptake. Inhibiting the complement pathway may be a strategy for reducing immunogenicity in AAV-based therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carola J. Maturana, Jessica L. Verpeut, Mahdi Kooshkbaghi, Esteban A. Engel
Summary: The study developed a tool to quantify the number of co-expressed AAV genomes in the nervous system. They found that different AAV vectors can efficiently co-express in the same neuron, which can be used for studying neuronal circuits, mapping brain connectivity, and treating genetic diseases affecting the nervous system.
Article
Biotechnology & Applied Microbiology
Oleksandr Kondratov, Liudmyla Kondratova, Ronald J. Mandel, Kirsten Coleman, Michael A. Savage, Heather L. Gray-Edwards, Timothy J. Ness, Edgar Rodriguez-Lebron, Robert D. Bell, Joseph Rabinowitz, Paul D. Gamlin, Sergei Zolotukhin
Summary: The study utilized a multiplex barcode recombinant AAV vector-tracing strategy to analyze 29 distinct AAV natural isolates and engineered capsids in the central nervous system of eight macaques, identifying the most efficient AAV capsid variants targeting specific CNS areas under different delivery routes. Newly developed bioinformatics and visualization algorithms for comparative analysis of mammalian brain models have been made publicly available.
Article
Oncology
Nadja Meumann, Christian Schmithals, Leroy Elenschneider, Tanja Hansen, Asha Balakrishnan, Qingluan Hu, Sebastian Hook, Jessica Schmitz, Jan Hinrich Braesen, Ann-Christin Franke, Olaniyi Olarewaju, Christina Brandenberger, Steven R. Talbot, Josef Fangmann, Ulrich T. Hacker, Margarete Odenthal, Michael Ott, Albrecht Piiper, Hildegard Buening
Summary: In this study, we report on the natural preference of adeno-associated virus serotype 2 (AAV2) vectors for hepatocellular carcinoma (HCC), which is due to the improved intracellular processing of AAV2 vectors in HCC, resulting in more vector genomes serving as templates for transcription. Therefore, AAV2 vectors can be used to strengthen current therapeutic approaches or develop novel strategies for treating HCC.
Article
Multidisciplinary Sciences
Qiang Wang, Lin Zhang, Guo-Wei Zhang, Jian-Hua Mao, Xiao-Dong Xi, Lu Jiang, Gang Lv, Jing Lu, Yan Shen, Zhu Chen, Jiang Zhu, Sai-Juan Chen
Summary: The study demonstrates that a single DNA cutting-mediated long-range replacement can restore the FIX-encoding function of a mutant F9 (mF9) carrying both regulatory and coding defects in a severe mouse HB model. It establishes an AAV/CRISPR-mediated gene-editing protocol applicable to complicated monogenetic disorders, underscoring the potentiality of improving therapeutic benefits through managing inflammation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Xuefeng Li, Xiaoli Wei, Jinduan Lin, Li Ou
Summary: Recombinant adeno-associated virus (AAV) has shown great potential as a delivery vehicle for gene therapy, but immune response issues need to be addressed for its effective clinical application.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Miranda Gehrke, Maria Diedrichs-Moehring, Jacqueline Bogedein, Hildegard Buning, Stylianos Michalakis, Gerhild Wildner
Summary: This study compared the immune responses of new AAV vectors with the parental AAV2 vector. The results showed that the new vectors were less sensitive to neutralizing antibodies and had similar cellular immune responses and cytokine production compared to the parental vector. Due to their enhanced retinal tropism, the new vectors are likely to have lower immunogenicity for gene therapy.
Article
Biochemistry & Molecular Biology
Mikako Wada, Naoya Uchida, Guillermo Posadas-Herrera, Hiromi Hayashita-Kinoh, Yuji Tsunekawa, Yukihiko Hirai, Takashi Okada
Summary: In this study, a large-scale short-term purification method for functional full-genome AAV particles was developed using 2-step cesium chloride (CsCl) density-gradient ultracentrifugation with a zonal rotor. The highly purified full-genome AAV particles were confirmed by various analytical techniques. The method showed effectiveness in gene therapy.
Article
Microbiology
Jakob Shoti, Keyun Qing, Arun Srivastava
Summary: Recombinant MV serotype vectors and their variants are being used in clinical trials for gene therapy for hemophilia. However, traditional liver-directed AAV gene therapy does not work in children with hemophilia. This study describes the development of an optimized human Factor IX gene expression cassette for potential gene therapy for hemophilia in children.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chady H. Hakim, Sandeep R. P. Kumar, Dennis O. Perez-Lopez, Nalinda B. Wasala, Dong Zhang, Yongping Yue, James Teixeira, Xiufang Pan, Keqing Zhang, Emily D. Million, Christopher E. Nelson, Samantha Metzger, Jin Han, Jacqueline A. Louderman, Florian Schmidt, Feng Feng, Dirk Grimm, Bruce F. Smith, Gang Yao, N. Nora Yang, Charles A. Gersbach, Shi-jie Chen, Roland W. Herzog, Dongsheng Duan
Summary: The study investigates the immune responses induced by AAV-CRISPR therapy in canine models of DMD, indicating that the Cas9-specific T cell response may pose a critical barrier to treatment.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Kun Wang, Ruolan Huang, Liyun Zhang, Dan Liu, Yong Diao
Summary: This study introduces an RAA-based assay for quick and accurate detection of AAV genome, improving the efficiency of AAV research and production.
Review
Immunology
David-Alexandre Gross, Novella Tedesco, Christian Leborgne, Giuseppe Ronzitti
Summary: One major goal of in vivo gene transfer is to achieve long-term expression of therapeutic genes. Adeno-associated viruses (AAV) have been widely used for gene transfer in multiple tissues. However, the immune response to AAV limits its application in a wider population. Strategies to overcome this limitation are being explored.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
A. Kagiava, J. Richter, C. Tryfonos, M. Leal-Julia, I. Sargiannidou, C. Christodoulou, A. Bosch, K. A. Kleopa
Summary: By comparing AAV serotypes and injection routes, it was found that AAVrh10 had higher biodistribution in Schwann cells compared to AAV9, but similar expression rates. Both intrathecal and intravenous injections were effective in transducing Schwann cells, with intrathecal injection potentially offering a more efficient treatment approach.
SCIENTIFIC REPORTS
(2021)
Review
Microbiology
Lena C. Schroeder, Derk Frank, Oliver J. Mueller
Summary: Cardiac-targeted transgene delivery provides new treatment opportunities for cardiovascular diseases by using cis-regulatory elements to restrict gene transfer and protect extracardiac organs. Tissue-specific promoters for targeted transcription in specific cardiac cells have been identified, some of which are induced at pathological states and could potentially act as induction-by-disease switches in gene therapy.
Article
Biochemistry & Molecular Biology
Tao Wang, Liang Yang, Mingjie Yuan, Charles R. Farber, Rosanne Spolski, Warren J. Leonard, Vijay C. Ganta, Brian H. Annex
Summary: Upregulation of IL-21R in endothelial cells from ischemic muscles can improve angiogenesis and perfusion recovery, while increased expression of miR-30b is shown to be both necessary and sufficient for IL21/IL-21R-mediated angiogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Retraction
Multidisciplinary Sciences
Giridhara R. Jayandharan, George Aslanidi, Ashley T. Martino, Stephan C. Jahn, George Q. Perrin, Roland W. Herzog, Arun Srivastava
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Biology
James E. Voss, Alicia Gonzalez-Martin, Raiees Andrabi, Roberta P. Fuller, Ben Murrell, Laura E. McCoy, Katelyn Porter, Deli Huang, Wenjuan Li, Devin Sok, Khoa Le, Bryan Briney, Morgan Chateau, Geoffrey Rogers, Lars Hangartner, Ann J. Feeney, David Nemazee, Paula Cannon, Dennis R. Burton
Article
Biotechnology & Applied Microbiology
Geoffrey L. Rogers, Hsu-Yu Chen, Heidy Morales, Paula M. Cannon
Letter
Biotechnology & Applied Microbiology
Geoffrey L. Rogers, Hsu-Yu Chen, Heidy Morales, Paula M. Cannon
Article
Oncology
Karina Krotova, Andrew Day, George Aslanidi
MOLECULAR THERAPY-ONCOLYTICS
(2019)
Article
Biotechnology & Applied Microbiology
Karina Krotova, George Aslanidi
HUMAN GENE THERAPY
(2020)
Article
Multidisciplinary Sciences
Karina Krotova, Nazli Khodayari, Regina Oshins, George Aslanidi, Mark L. Brantly
SCIENTIFIC REPORTS
(2020)
Review
Biotechnology & Applied Microbiology
Geoffrey L. Rogers, Paula M. Cannon
Summary: Cell therapies based on reprogrammed adaptive immune cells have great potential as living drugs. Engineered B cells also have the potential to be developed as immune cell therapies, but engineering their specificity and functionality is more challenging than for T cells. Recent advances in genome editing are now allowing reprogramming of B cells by site-specific engineering of the Ig locus with preformed antibodies.
Article
Medicine, Research & Experimental
Geoffrey L. Rogers, Chun Huang, Robert D. E. Clark, Eduardo Seclen, Hsu-Yu Chen, Paula M. Cannon
Summary: By optimizing ex vivo culture conditions, the study demonstrates that using a high concentration of AAV6 for a short transduction time combined with electroporation can improve genome editing rates in human CD4+ T cells and B cells, reducing cellular toxicity and decreasing the amount of AAV6 required.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Medicine, Research & Experimental
Karina Krotova, Hisae Kuoch (Yoshitomi), Colin Caine, George Aslanidi
Summary: This study further elucidated the mechanism of a novel AAV-based vaccine, which inhibits tumor growth by optimizing AAV vectors and gene expression. The vaccine induced cellular and humoral antigen-specific immune responses and the temporal expression of antigen coincided with T cell infiltration. Our data demonstrated the superior protective immune response of optimized AAV6-TRP1 compared to other self-antigens.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Hisae Kuoch, Karina Krotova, Melanie L. Graham, Mark L. Brantly, George Aslanidi
Summary: Accurate assessment of AAV-specific pre-existing humoral immunity is crucial for effective use of clinical gene therapy. This study presents a method that applies equivalent infection conditions to each AAV serotype and validates it through evaluating neutralizing antibody titers in human donors, dogs, and non-human primates. The method allows for rapid and accurate evaluation of neutralizing titers for individual subjects, aiding clinical enrollment and the selection of the most suitable AAV serotype for each patient.
Meeting Abstract
Biotechnology & Applied Microbiology
P. E. Cruz, C. Ceballos, V. Truong, A. Rosario, X. Liu, S. Modrow, M. Parianos, V. Richards, J. Lew, E. Rostonic, K. Schob, M. Pardo, D. Deng, C. Croft, J. Ayer, G. Aslanidi, T. E. Golde
HUMAN GENE THERAPY
(2018)
Meeting Abstract
Immunology
Karina Krotova, Nazli Khodayari, Regina Oshins, George Aslanidi, Mark Brantly
JOURNAL OF IMMUNOLOGY
(2018)
Meeting Abstract
Biotechnology & Applied Microbiology
Yenerys Colon-Cortes, Mutasim Abu Hasan, George Aslanidi
Meeting Abstract
Biotechnology & Applied Microbiology
Yenerys Colon-Cortes, Nathalie Baumlin-Schmid, Neeraj Sharma, Jung Soo Suk, Garry Cutting, Matthias A. Salathe, Mutasim Abu Hasan, George Aslanidi