Small interfering RNA (siRNA) in dyslipidemia: a systematic review on safety and efficacy of siRNA
Open accessAbstract
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.
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A broader systematic review of siRNA therapies in dyslipidemia reported heterogeneous lipid effects across targets, but did not provide quantitative comparisons.
“A broader systematic review of siRNA therapies in dyslipidemia reported heterogeneous lipid effects across targets, but did not provide quantitative comparisons (Alla et al., 2025).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Alla et al., 2025
The Discussion and Methods > Eligibility Criteria cover siRNA therapies targeting several lipid-related genes, and the Limitations describe heterogeneity between studies. But the review does provide numerical lipid-effect results and compares reductions among therapies in the Discussion. It does not appear to present a formal quantitative comparison across targets, so the unqualified statement that it provided no quantitative comparisons overstates the point. The indexed passages do not supply page numbers. (LLM, conf=0.84)
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Gao, Y., Bai, Y., Mu, X., & Pang, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1736821 · Cited by 4 · see citing works
“A broader systematic review of siRNA therapies in dyslipidemia reported heterogeneous lipid effects across targets, but did not provide quantitative comparisons (Alla et al., 2025).”
Tawfik, S. M., Nguyen, L. T. G., Jin, J., Armanios, B., & Zhong, X.-B. (2025) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2025.103802 · Cited by 1 · see citing works
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Gene Therapy for Lipid Management: Dawn of a New Era
Manoria, P. C. (2026) · Cureus · doi:10.7759/cureus.112496
- Authors
- Alla, S. S. M., Shah, D. J., Meyur, S., Agarwal, P., Alla, D., Moraboina, S. L., Ghadvaje, G. V., Bayeh, R. G., Malireddi, A., Shajan, T., Vineetha, B., Sai Prudhvi, T., & Biziyaremye, P.
- Affiliations
- Andhra University (IN)
- Massachusetts College of Pharmacy and Health Sciences (US)
- AMA School of Medicine (PH)
- Portsmouth Regional Hospital (US)
- Apollo Institute of Medical Sciences & Research (IN)
- Smolensk State Medical University (RU)
- Adama Hospital Medical College (ET)
- University of Rwanda (RW)
- Corresponding author
- Biziyaremye, Patrick
- ORCID
- Venue
- Journal of Experimental Pharmacology
- Publisher
- Informa UK Limited
- Published
- 2025-05
- Volume
- Volume 17
- Pages
- 249-267
- ISSN
- 1179-1454 (ISSN-L)
- PMC
- PMC12126973
- OpenAlex
- W4410772497
- Cited by
- 4
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Experimental Pharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- siRNA, RNA interference therapy, dyslipidemia, inclisiran, olpasiran, plozasiran, hypercholesterolemia, type IV hyperlipoproteinemia, hypertriglyceridemia, mixed dyslipidemia, chylomicronemia, LDL cholesterol lowering, adverse effects, new-onset diabetes, nasopharyngitis
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