“…137 Likewise, neonatal Fc receptor inhibition with monoclonal antibodies, similarly based upon the principle of temporarily reducing IgG levels, appeared effective in overcoming NAbs in mice and nonhuman primates. 138 It is important to note that individuals with humoral responses against AAV are likely to also possess anti-AAV cellular immunity, which too may have crucial effects on therapeutic efficacy. For example, cytotoxic T cell-mediated destruction of transduced hepatocytes has been attributed as one of the main reasons for the therapeutic failures observed in some of the hemophilia trials.…”
Section: Safety Aspects Of Aav-based Therapy Risks Of Immunogenicity ...mentioning
confidence: 99%
“…137 Likewise, neonatal Fc receptor inhibition with monoclonal antibodies, similarly based upon the principle of temporarily reducing IgG levels, appeared effective in overcoming NAbs in mice and nonhuman primates. 138…”
Section: Safety Aspects Of Aav-based Therapymentioning
Peripheral artery disease (PAD) is a vascular disorder caused by occlusive atherosclerosis, which commonly impairs blood flow to the lower extremities. The prevalence of PAD is increasing globally with >200 million people affected. PAD remains a growing global health problem as the population continues to age and diabetes incidence grows. Many patients with PAD, most notably those with critical limb ischemia, fail attempts at surgical and percutaneous intervention to improve blood flow and are at risk of amputation. Gene therapy provides an opportunity to change the clinical course of PAD in these patients via strategies that increase vascular supply through angiogenesis and arteriogenesis improving muscle perfusion and function in ischemic legs. This article discusses gene therapy approaches in the context of PAD, both intermittent claudication and critical limb ischemia, and the promise of adeno-associated virus–based strategies delivering not just VEGFs (vascular endothelial growth factors) but a range of other mediators as potential new therapeutics. We also highlight challenges and failures in the clinical translation of gene therapy for PAD and how at least some of these obstacles may be overcome using adeno-associated virus.
“…137 Likewise, neonatal Fc receptor inhibition with monoclonal antibodies, similarly based upon the principle of temporarily reducing IgG levels, appeared effective in overcoming NAbs in mice and nonhuman primates. 138 It is important to note that individuals with humoral responses against AAV are likely to also possess anti-AAV cellular immunity, which too may have crucial effects on therapeutic efficacy. For example, cytotoxic T cell-mediated destruction of transduced hepatocytes has been attributed as one of the main reasons for the therapeutic failures observed in some of the hemophilia trials.…”
Section: Safety Aspects Of Aav-based Therapy Risks Of Immunogenicity ...mentioning
confidence: 99%
“…137 Likewise, neonatal Fc receptor inhibition with monoclonal antibodies, similarly based upon the principle of temporarily reducing IgG levels, appeared effective in overcoming NAbs in mice and nonhuman primates. 138…”
Section: Safety Aspects Of Aav-based Therapymentioning
Peripheral artery disease (PAD) is a vascular disorder caused by occlusive atherosclerosis, which commonly impairs blood flow to the lower extremities. The prevalence of PAD is increasing globally with >200 million people affected. PAD remains a growing global health problem as the population continues to age and diabetes incidence grows. Many patients with PAD, most notably those with critical limb ischemia, fail attempts at surgical and percutaneous intervention to improve blood flow and are at risk of amputation. Gene therapy provides an opportunity to change the clinical course of PAD in these patients via strategies that increase vascular supply through angiogenesis and arteriogenesis improving muscle perfusion and function in ischemic legs. This article discusses gene therapy approaches in the context of PAD, both intermittent claudication and critical limb ischemia, and the promise of adeno-associated virus–based strategies delivering not just VEGFs (vascular endothelial growth factors) but a range of other mediators as potential new therapeutics. We also highlight challenges and failures in the clinical translation of gene therapy for PAD and how at least some of these obstacles may be overcome using adeno-associated virus.
“…In one of their recent publications, Wilson's team explored the role of Neonatal Fc receptor (FcRn) in AAV-based gene therapies, highlighting its impact on neutralizing antibodies (NAbs). They assessed the efficacy of an FcRn-inhibiting monoclonal antibody (M281) to improve AAV-based therapies in patients with pre-existing immunity (Horiuchi et al, 2023). On the other hand, Samulski, R. Jude had the most total citations and cocitations, and his recent review highlighted advancements in AAV vectors for gene therapy, providing valuable insights into the current state of AAV-based gene therapies (Pupo et al, 2022).…”
BackgroundGene therapy involves introducing and editing foreign genes in the body to treat and prevent genetic diseases. Adeno-associated virus (AAV) vector has become a widely used tool in gene therapy due to its high safety and transfection efficiency.MethodsThis study employs bibliometric analysis to explore the foundation and current state of AAV vector application in gene therapy research. A total of 6,069 publications from 1991 to 2022 were analyzed, retrieved from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WoSCC) of Clarivate Analytics. Institutions, authors, journals, references, and keywords were analyzed and visualized by using VOSviewer and CiteSpace. The R language and Microsoft Excel 365 were used for statistical analyses.ResultsThe global literature on AAV vector and gene therapy exhibited consistent growth, with the United States leading in productivity, contributing 3,868 papers and obtaining the highest H-index. Noteworthy authors like Wilson JM, Samulski RJ, Hauswirth WW, and Mingozzi F were among the top 10 most productive and co-cited authors. The journal “Human Gene Therapy” published the most papers (n = 485) on AAV vector and gene therapy. Current research focuses on “gene editing,” “gene structure,” “CRISPR,” and “AAV gene therapy for specific hereditary diseases.”ConclusionThe application of AAV vector in gene therapy has shown continuous growth, fostering international cooperation among countries and institutions. The intersection of gene editing, gene structure, CRISPR, and AAV gene therapy for specific hereditary diseases and AAV vector represents a prominent and prioritized focus in contemporary gene therapy research. This study provides valuable insights into the trends and characteristics of AAV gene therapy research, facilitating further advancements in the field.
“…121 More recently, an additional strategy has been described that utilizes neonatal Fc receptor inhibition to enable AAV gene therapy even in the presence of pre-existing humoral immunity. 122 Figure 4 Strategies for dampening the host humoral immune response to AAV vectors ① Transient depletion of B lymphocytes using CD20 antibody, ② AAV D-sequence-mediated suppression of MHC class II gene expression, and ③ transient degradation of pre-existing IgG antibodies using IgG-cleaving IdeS and IdeZ bacterial endopeptidases. Modified image from.…”
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