A systematic review and meta-analysis of immunosuppressive regimens and immune-related outcomes in adeno-associated virus-based gene therapy
Abstract
Significant progress has been made in adeno-associated virus (AAV)-based gene therapy. However, host immune responses remain a major challenge to its widespread clinical application, making immunosuppressive regimens an important component of clinical management. We performed a systematic review and meta-analysis to characterize immunosuppressive regimens and immune-related outcomes in clinical AAV gene therapy. The primary outcomes were the proportions of humoral immune responses, gene therapy-associated uveitis (GTAU), elevated alanine aminotransferase (ALT), and elevated creatine kinase (CK). A total of 73 studies involving 1773 participants were included and categorized as ocular (n = 31), liver (n = 22), muscle (n = 12), or central nervous system (n = 8) according to the primary target organ. Primary subgroup analyses were restricted to studies in which immunosuppression was used prophylactically. The pooled proportions of humoral immune responses were 27.7%, 75.8%, 35.2%, and 42.6% for ocular-, liver-, muscle-, and central nervous system-directed AAV gene therapy, respectively. The pooled proportions of GTAU in ocular-directed studies, elevated ALT in liver-directed studies, elevated CK in muscle-directed studies, and elevated ALT in central nervous system-directed studies were 24.2%, 49.5%, 5.1%, and 16.5%, respectively. Statistically significant regimen-based subgroup differences were observed for GTAU in ocular-directed studies and for humoral immune responses in muscle-directed studies. However, the current evidence does not establish the superiority of any specific immunosuppressive regimen. These findings highlight variation in immune-related outcomes across target organs and the need for more clinical studies with standardized outcome reporting to better inform immunosuppressive strategies in AAV gene therapy.
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BibTeX
@article{wang2026systematic,
title = {{A systematic review and meta-analysis of immunosuppressive regimens and immune-related outcomes in adeno-associated virus-based gene therapy}},
author = {Ziyang Wang and Ni Wu and Diyi Fu and Qian Zhao and Hongyun Wang},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-71872-w},
url = {https://www.nature.com/articles/s41598-026-71872-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A systematic review and meta-analysis of immunosuppressive regimens and immune-related outcomes in adeno-associated virus-based gene therapy
AU - Ziyang Wang
AU - Ni Wu
AU - Diyi Fu
AU - Qian Zhao
AU - Hongyun Wang
PY - 2026
DA - 2026/10/01
JO - Scientific Reports
DO - 10.1038/s41598-026-71872-w
UR - https://www.nature.com/articles/s41598-026-71872-w
AB - Significant progress has been made in adeno-associated virus (AAV)-based gene therapy. However, host immune responses remain a major challenge to its widespread clinical application, making immunosuppressive regimens an important component of clinical management. We performed a systematic review and meta-analysis to characterize immunosuppressive regimens and immune-related outcomes in clinical AAV gene therapy. The primary outcomes were the proportions of humoral immune responses, gene therapy-associated uveitis (GTAU), elevated alanine aminotransferase (ALT), and elevated creatine kinase (CK). A total of 73 studies involving 1773 participants were included and categorized as ocular (n = 31), liver (n = 22), muscle (n = 12), or central nervous system (n = 8) according to the primary target organ. Primary subgroup analyses were restricted to studies in which immunosuppression was used prophylactically. The pooled proportions of humoral immune responses were 27.7%, 75.8%, 35.2%, and 42.6% for ocular-, liver-, muscle-, and central nervous system-directed AAV gene therapy, respectively. The pooled proportions of GTAU in ocular-directed studies, elevated ALT in liver-directed studies, elevated CK in muscle-directed studies, and elevated ALT in central nervous system-directed studies were 24.2%, 49.5%, 5.1%, and 16.5%, respectively. Statistically significant regimen-based subgroup differences were observed for GTAU in ocular-directed studies and for humoral immune responses in muscle-directed studies. However, the current evidence does not establish the superiority of any specific immunosuppressive regimen. These findings highlight variation in immune-related outcomes across target organs and the need for more clinical studies with standardized outcome reporting to better inform immunosuppressive strategies in AAV gene therapy.
SN - 2045-2322
ER -