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Progress on siRNA-based gene therapy targeting secondary injury after intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a life-threatening condition with a high mortality rate. For survivors, quality of life is determined by primary and secondary phases of injury. The prospects for injury repair and recovery after ICH are highly dependent on the extent of secondary injury. Currently, no effective treatments are available to prevent secondary injury or its long-term effects. One promising strategy that has recently garnered attention is gene therapy, in particular, small interfering RNAs (siRNA), which silence specific genes responsible for destructive effects after hemorrhage. Gene therapy as a potential treatment for ICH is being actively researched in animal studies. However, there are many barriers to the systemic delivery of siRNA-based therapy, as the use of naked siRNA has limitations. Recently, the Food and Drug Administration approved two siRNA-based therapies, and several are undergoing Phase 3 clinical trials. In this review, we describe the advancements in siRNA-based gene therapy for ICH and also summarize its advantages and disadvantages.

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Fig. 1: Signaling pathways following hemorrhagic stroke.

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Funding

Daniyah Almarghalani was supported by a scholarship from Taif University, Saudi Arabia Cultural Mission. The study was partly supported by grants from the American Heart Association #17AIREA33700076/ZAS/2017 and National Institute of Neurological Disorders and Stroke of the National Institutes of Health #R01NS112642 to ZAS.

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DAA contributed to performing the literature search, designing the review structure, and writing the first draft. ZAS contributed to reviewing, providing feedback, and approving the final draft.

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Correspondence to Zahoor A. Shah.

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Almarghalani, D.A., Shah, Z.A. Progress on siRNA-based gene therapy targeting secondary injury after intracerebral hemorrhage. Gene Ther (2021). https://doi.org/10.1038/s41434-021-00304-3

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