Review
Immunology
Hildegund C. J. Ertl
Summary: Adeno-associated virus (AAV)-mediated gene transfer has shown benefits in treating patients with inherited diseases like hemophilia B, but challenges remain due to potential rejection of AAV-transduced cells. Immunosuppression may prevent rejection in some patients. CD8(+) T cells induced by AAV infections may recognize AAV vector's capsids and eliminate cells expressing degraded capsid antigens, or AAV vectors themselves may induce de novo T cell responses, particularly at high doses. This chapter discusses strategies to prevent activation of CD8(+) T cell responses to AAV infections and gene transfer.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Bradley A. Hamilton, J. Fraser Wright
Summary: This article discusses the host immune responses that limit durable therapeutic gene expression in AAV-based human gene therapies. A strategy of removing pathogen-associated molecular patterns in AAV vector genomes to overcome immunological barriers is proposed.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
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
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
Biology
Michael Whitehead, Andrew Osborne, Patrick Yu-Wai-Man, Keith Martin
Summary: Viral vectors like AAV are effective for gene therapy, but pre-existing and induced NAbs in humans can limit their efficiency. Overcoming NAb responses remains a challenge, with successful translation of strategies into clinical practice still limited.
BIOLOGICAL REVIEWS
(2021)
Article
Immunology
Thais B. Bertolini, Jamie L. Shirley, Irene Zolotukhin, Xin Li, Tsuneyasu Kaisho, Weidong Xiao, Sandeep R. P. Kumar, Roland W. Herzog
Summary: AAV vectors are promising for gene therapy, but immune responses can occur due to CpG motifs in the vector genome, leading to CD8(+) T cell activation. Depletion of CpG motifs can reduce such immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Biotechnology & Applied Microbiology
Coralie Croissant, Joshua Armitano, Bertrand Lazuech, Danijel Svec, Cyril Pugin, Anais Guesdon, Louise Bryan, Antonio Castro, Lea Neuhaus, Giulia Fonti, Jacopo Martinis, Maria J. Wurm, Florian M. Wurm, Paco Pino
Summary: We developed a new T-antigen-negative HEK cell line, called HEKzeroT, using the CRISPR-Cas9 strategy. This cell line showed no impact on cell growth, viability, and productivity, and was able to produce high AAV titers.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Medicine, Research & Experimental
Dongxin Wang, Qungang Zhou, Xiang Qiu, Xiaomei Liu, Chun Zhang
Summary: This study optimized the protocol for rAAV6 transduction of primary T cells, significantly improved the expression efficiency of the rAAV6 delivered CAR gene, and successfully generated rAAV6-based CAR-T cells (AAV-CAR-T). The findings provide an efficient method for AAV transduction of T cells and an alternative way for the preparation of CAR-T cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Victoria G. Hall, Victor H. Ferreira, Heidi Wood, Matthew Ierullo, Beata Majchrzak-Kita, Kathy Manguiat, Alyssia Robinson, Vathany Kulasingam, Atul Humar, Deepali Kumar
Summary: Delayed dosing intervals can enhance immune response to COVID-19 vaccination, including virus neutralization against wild-type and variant viruses. This finding has significant implications for the global implementation of vaccines.
Article
Immunology
Carlos A. Brito-Sierra, Megan B. Lannan, Robert W. Siegel, Laurent P. Malherbe
Summary: Using MHC-associated peptide proteomics, researchers identified the HLA-DR and HLA-DQ immunopeptidomes of three different AAV serotypes, revealing multiple promiscuous peptides with cross-reactivity. Despite high sequence homology, there were few identical peptides among the immunopeptidomes of AAV2, AAV6, and AAV9.
FRONTIERS IN IMMUNOLOGY
(2022)
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.
Review
Pharmacology & Pharmacy
Marthe T. van Daal, Gert Folkerts, Johan Garssen, Saskia Braber
Summary: The increase in noncommunicable diseases (NCDs) is largely attributed to lifestyle factors, particularly dietary habits. High intake of saturated fatty acids and low intake of dietary fiber are linked to the rise in NCDs, while a low intake of saturated fats and a high intake of dietary fiber have a protective effect. Nutritional components can activate specific receptors which modulate the immune system, potentially offering insights for preventing and treating NCDs.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Engineering, Biomedical
Yue Gao, Zhijun Ouyang, Chao Yang, Cong Song, Chunjuan Jiang, Shaoli Song, Minguiu Shen, Xiangyang Shi
Summary: A novel dendrimer-based nanohybrid platform is developed for dual-mode CT/MR imaging-guided cancer immunotherapy by regulating T cell exhaustion, showing promising potential for overcoming immune escape of cancer cells and improving the efficiency of cancer immunotherapy.
ADVANCED HEALTHCARE MATERIALS
(2021)