Pre-Clinical Studies of MicroRNA-Based Therapies for Sepsis: A Scoping Review

Abstract

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential.

Keywords

• sepsis
• microRNAs
• inhibitors
• mimics
• antagomirs
• infection