Journey of siRNA: Clinical Developments and Targeted Delivery
- PMID:29584585
- DOI: 10.1089/nat.2017.0715
Journey of siRNA: Clinical Developments and Targeted Delivery
Abstract
Since the evolutionary discovery of RNA interference and its utilization for gene knockdown in mammalian cell, a remarkable progress has been achieved in small interfering RNA (siRNA) therapeutics. siRNA is a promising tool, utilized as therapeutic agent against various diseases. Despite its significant potential benefits, safe, efficient, and target oriented delivery of siRNA is one of the major challenges in siRNA therapeutics. This review covers major achievements in clinical trials and targeted delivery of siRNAs using various targeting ligand-receptor pair. Local and systemically administered siRNA drug candidates at various phases in clinical trials are described in this review. This review also provides a deep insight in development of targeted delivery of siRNA. Various targeting ligand-siRNA pair with complexation and conjugation approaches are discussed in this review. This will help to achieve further optimization and development in targeted delivery of siRNAs to achieve higher gene silencing efficiency with lowest siRNA dose availability.
Keywords: GalNAc; RNA interference; clinical trial; gene silencing; siRNA; targeted delivery.
Similar articles
- siRNA therapeutics: a clinical reality.Saw PE, Song EW.Saw PE, et al.Sci China Life Sci. 2020 Apr;63(4):485-500. doi: 10.1007/s11427-018-9438-y. Epub 2019 Apr 30.Sci China Life Sci. 2020.PMID:31054052Review.
- Therapeutic face of RNAi: in vivo challenges.Borna H, Imani S, Iman M, Azimzadeh Jamalkandi S.Borna H, et al.Expert Opin Biol Ther. 2015 Feb;15(2):269-85. doi: 10.1517/14712598.2015.983070. Epub 2014 Nov 15.Expert Opin Biol Ther. 2015.PMID:25399911Review.
- siRNA: novel therapeutics from functional genomics.Joshi BH, Pachchigar KP.Joshi BH, et al.Biotechnol Genet Eng Rev. 2014 Oct;30(1-2):1-30. doi: 10.1080/02648725.2014.921495.Biotechnol Genet Eng Rev. 2014.PMID:25023460Review.
- Functional nanostructures for effective delivery of small interfering RNA therapeutics.Hong CA, Nam YS.Hong CA, et al.Theranostics. 2014 Sep 19;4(12):1211-32. doi: 10.7150/thno.8491. eCollection 2014.Theranostics. 2014.PMID:25285170Free PMC article.Review.
- The cutting-edge technologies of siRNA delivery and their application in clinical trials.Lee K, Jang B, Lee YR, Suh EY, Yoo JS, Lee MJ, Lee JY, Lee H.Lee K, et al.Arch Pharm Res. 2018 Sep;41(9):867-874. doi: 10.1007/s12272-018-1069-4. Epub 2018 Aug 22.Arch Pharm Res. 2018.PMID:30136248Review.
Cited by
- Introducing an In Vitro Liver Stability Assay Capable of Predicting the In Vivo Pharmacodynamic Efficacy of siRNAs for IVIVC.Basiri B, Xie F, Wu B, Humphreys SC, Lade JM, Thayer MB, Yamaguchi P, Florio M, Rock BM.Basiri B, et al.Mol Ther Nucleic Acids. 2020 Sep 4;21:725-736. doi: 10.1016/j.omtn.2020.07.012. Epub 2020 Jul 10.Mol Ther Nucleic Acids. 2020.PMID:32771924Free PMC article.
- Supportive Oligonucleotide Therapy (SOT) as an Alternative Treatment Option in Cancer: A Preliminary Study.Papasotiriou I, Beis G, Iliopoulos AC, Apostolou P.Papasotiriou I, et al.In Vivo. 2022 Mar-Apr;36(2):898-906. doi: 10.21873/invivo.12779.In Vivo. 2022.PMID:35241548Free PMC article.
- siRNA-based nanotherapeutics as emerging modalities for immune-mediated diseases: A preliminary review.Sargazi S, Arshad R, Ghamari R, Rahdar A, Bakhshi A, Karkan SF, Ajalli N, Bilal M, Díez-Pascual AM.Sargazi S, et al.Cell Biol Int. 2022 Sep;46(9):1320-1344. doi: 10.1002/cbin.11841. Epub 2022 Jul 13.Cell Biol Int. 2022.PMID:35830711Free PMC article.Review.
- PD-L1 siRNA-mediated silencing in acute myeloid leukemia enhances anti-leukemic T cell reactivity.van Ens D, Mousset CM, Hutten TJA, van der Waart AB, Campillo-Davo D, van der Heijden S, Vodegel D, Fredrix H, Woestenenk R, Parga-Vidal L, Jansen JH, Schaap NPM, Lion E, Dolstra H, Hobo W.van Ens D, et al.Bone Marrow Transplant. 2020 Dec;55(12):2308-2318. doi: 10.1038/s41409-020-0966-6. Epub 2020 Jun 11.Bone Marrow Transplant. 2020.PMID:32528120
- Formulation-based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives.Sallam MA, Prakash S, Kumbhojkar N, Shields CW 4th, Mitragotri S.Sallam MA, et al.Bioeng Transl Med. 2021 May 4;6(3):e10215. doi: 10.1002/btm2.10215. eCollection 2021 Sep.Bioeng Transl Med. 2021.PMID:34589595Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical