Small Interfering RNA (siRNA) in Dyslipidemia: A Systematic Review on Safety and Efficacy of siRNA

Sai Santhosha Mrudula Alla,1 Dhruv Jayeshkumar Shah,2 Shourya Meyur,3 Pahel Agarwal,4 Deekshitha Alla,1 Sai Lokesh Moraboina,5 Gayatri Vijay Ghadvaje,6 Ruth Getaneh Bayeh,7 Aparna Malireddi,1 Tess Shajan,8 Bodipudi Vineetha,5 Thalvayapati Sai Prudhvi,9 Patrick Biziyaremye10 1Department of General Medicine, Andhra Medical College, Visakhapatnam, India; 2Department of General Medicine, Massachusetts College of Pharmacy and Health Sciences (MCPHS), Boston, MA, USA; 3Department of General Medicine, AMA School of Medicine, Makati City, Philippines; 4Department of Internal Medicine, Portsmouth Regional Hospital, Portsmouth, NH, USA; 5Department of General Medicine, Apollo Institute of Medical Sciences and Research, Chittoor, India; 6Department of General Medicine, Smolensk State Medical University, Smolensk, Russia; 7Department of General Medicine, Adama General Hospital and Medical College, Adama, Ethiopia; 8Department of General Medicine, p k Das Institute of Medical Sciences, Palakkad, India; 9Department of General Medicine, Government Kilpauk Medical College, Chennai, India; 10Department of General Medicine, University of Rwanda, Kigali, RwandaCorrespondence: Patrick Biziyaremye, University of Rwanda, Kigali, Rwanda, Email [email protected]: RNA interference (RNAi) therapy represents an evolving advancement in the management of dyslipidemia. One prominent form of RNAi therapy is small interfering RNA (siRNA), which has emerged as a promising therapeutic strategy. This study aims to critically analyze the efficacy and safety of siRNA in the treatment of dyslipidemia.Methods: PubMed, Scopus, and Web of Science servers were used to conduct a systematic search in compliance with the PRISMA guidelines.Results: A total of 20 studies with 6651 participants were included in the analysis. The drugs used in the studies were. Inclisiran led to a notable 44.09% reduction in LDL and 37.5% in apolipoprotein levels among individuals with hypercholesterolemia. In hyperlipoproteinemia(a), therapies like Lepodisiran and Olpasiran achieved a 75.69% drop in apolipoproteins and 16.25% in LDL. For hypertriglyceridemia, agents such as ARO-APOC3 and Plozasiran showed over 50% reductions in both VLDL and triglycerides. In mixed hyperlipidemia and chylomicronemia, Plozasiran significantly reduced triglycerides by up to 79% and apolipoproteins by 87.5%. The 5 most common adverse effects reported were nasopharyngitis, diabetes mellitus (including new-onset diabetes mellitus and worsening diabetes mellitus), injection site adverse effects, back pain, and hypertension.Conclusion: In conclusion, the benefits of siRNA therapy in dyslipidemia management appear to outweigh its potential drawbacks, demonstrating promising efficacy and safety profiles. However, further research is necessary to fully understand its long-term effects and optimize its therapeutic potential.Keywords: small interfering RNA, RNA interference therapy, inclisiran, ALN-PCS, ARO ANG3, lipodisiran, zerlasiran, Plozasiran, zodasiran, ARO-APOC3, SLN360, olpasiran