Lentivirus- or AAV-mediated gene therapy interventions in ischemic stroke: A systematic review of preclinical in vivo studies

Scientific paper - Review paper

• Author: Laura Skukan
• Author: Matea Brezak
• Author: Rok Ister
• Author: Lars Klimaschewski
• Author: Aleksandar Vojta
• Author: Vlatka Zoldoš
• Author: Srećko Gajović
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Histology and Embryology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience

Abstract (english)

Due to the limited therapeutic options after ischemic stroke, gene therapy has emerged as a promising choice, especially with recent advances in viral vector delivery systems. Therefore, we aimed to provide the current state of the art of lentivirus (LV) and adeno-associated virus (AAV) mediated gene interventions in preclinical ischemic stroke models. A systematic analysis including qualitative and quantitative syntheses of studies published until December 2020 was performed. Most of the 87 selected publications used adult male rodents and the preferred stroke model was transient middle cerebral artery occlusion. LV and AAV vectors were equally used for transgene delivery, however loads of AAVs were higher than LVs. Serotypes having broad cell tropism, the use of constitutive promoters, and virus delivery before the stroke induction via stereotaxic injection in the cortex and striatum were preferred in the analyzed studies. The meta-analysis based on infarct volume as the primary outcome confirmed the efficacy of the preclinical interventions. The quality assessment exposed publication bias and setbacks in regard to risks of bias and study relevance. The translational potential could increase by using specific cell targeting, post-stroke interventions, non-invasive systematic delivery, and use of large animals.

• Keywords (english): Animals; Cerebral Cortex / blood supply; Cerebral Cortex / metabolism; Corpus Striatum / blood supply; Corpus Striatum / metabolism; Dependovirus; Disease Models, Animal; Genetic Therapy; Genetic Vectors; Humans; Ischemic Stroke / genetics; Ischemic Stroke / metabolism; Ischemic Stroke / therapy; Lentivirus
• Language: english
• Publication type: Scientific paper - Review paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Journal of Cerebral Blood Flow & Metabolism
• Numbering: vol. 42, no. 2, pp. 219-236
• p-ISSN: 0271-678X
• e-ISSN: 1559-7016
• DOI: https://doi.org/10.1177/0271678X211039997
• URN:NBN: urn:nbn:hr:105:642820
• Publication: 2022-02
• Document URL: http://journals.sagepub.com/doi/10.1177/0271678X211039997
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-05-13 07:46:26