Small Interfering RNA (siRNA) Therapy: Gene Therapy for Inherited Diseases-An Updated Review for Healthcare Professionals | ||
| Egyptian Journal of Chemistry | ||
| Volume 68, Issue 13, December 2025, Pages 1235-1246 PDF (500.18 K) | ||
| Document Type: Review Articles | ||
| DOI: 10.21608/ejchem.2025.412143.12157 | ||
| Authors | ||
| Qadsyah Ali Aladaili* ; Jumanah Abdulaziz Alluhaydan; Rana Mohammed Alsuliman; Wedad Shilash Alanazi; Fatimah Khalid Alkhunaizi; Munira Hathal Alotaibi; Reem Saleh Alonazi; Amal Alhumidy Alanazi; Mesfer Mohammed Alshayi; Raghad Abdullah Alwthinani; Mishary Abdullah Alajery; Ghadeer Ghazi Alkhabbaz; Malak Ibrahim Allaythi; Abdulrahman Marzooq Alharbi; Asma Yahya Logabi; Bayan Abdalrhman Bafrhan | ||
| Ministry of National Guard, Saudi Arabia | ||
| Abstract | ||
| Background: Small interfering RNA (siRNA) medicines have progressed from proof-of-concept to clinical reality, culminating in six U.S. FDA-approved agents that silence hepatic transcripts driving amyloid neuropathy, porphyria, hyperoxaluria, and atherogenic dyslipidemia. Aim: To synthesize up-to-date knowledge on the therapeutic class, detailing mechanisms, indications, dosing, safety, and monitoring. Methods: Structured narrative review of the supplied article integrating mechanistic principles of RNA interference, regimen specifics, adverse-event profiles, contraindications, and practice-based monitoring. Results: Patisiran (LNP-delivered) and GalNAc-conjugated givosiran, lumasiran, inclisiran, nedosiran, and vutrisiran exploit dicer/RISC-mediated cleavage of target mRNAs (TTR, ALAS1, HAO1, PCSK9, LDHA), achieving durable protein knockdown. Administration spans intravenous infusion (patisiran) and infrequent subcutaneous regimens (others), with weight-based loading for select pediatric indications. Class-specific risks include infusion reactions (patisiran) and injection-site reactions; agent-specific signals include transaminase elevation, renal indices and hyperhomocysteinemia (givosiran), and vitamin A depletion requiring supplementation (vutrisiran). Hypersensitivity to givosiran is an absolute contraindication. Conclusion: siRNA therapeutics deliver mechanism-based control of diverse inherited and cardiometabolic diseases through precise, durable transcript silencing; safe implementation hinges on route-appropriate administration, proactive laboratory surveillance, nutritional stewardship where relevant, and standardized algorithms for missed doses and dose modification | ||
| Keywords | ||
| small interfering RNA; patisiran; givosiran; lumasiran; inclisiran; safety and efficacy | ||
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