title: Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.
abstract: RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.
authors.affiliation: Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yinjian
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: weixx@sun5.ibp.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D018390:Gene Targeting; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000097:blood / Q000235:genetics; D013678:Technology, Pharmaceutical; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering
keywords: Barriers; Clinical trials; Off-target effect; RNAi therapeutics; siRNA delivery