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Review
. 2025 May 28:17:249-267.
doi: 10.2147/JEP.S521579. eCollection 2025.

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 Biziyaremye  10
Affiliations
Review

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

Sai Santhosha Mrudula Alla et al. J Exp Pharmacol. .

Abstract

Introduction: 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: ALN-PCS; ARO ANG3; ARO-APOC3; Plozasiran; RNA interference therapy; SLN360; inclisiran; lipodisiran; olpasiran; small interfering RNA; zerlasiran; zodasiran.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Search results from different databases.
Figure 2
Figure 2
Drugs under siRNA target various lipid synthesis genes.
See this image and copyright information in PMC

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