title: New paradigms on siRNA local application.
abstract: Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in the mRNA's degradation. It is a potential therapeutic approach for many diseases caused by altered gene expression. The delivery of siRNA is still a major problem due to its rapid degradation in the circulation. Various strategies have been proposed to help with the cellular uptake of siRNA and short or small hairpin RNA (shRNA). Here, we reviewed recently published data regarding local applications of siRNA. Compared with systemic delivery methods, local delivery of siRNA/shRNA has many advantages, such as targeting the specific tissues or organs, mimicking a gene knockout effect, or developing certain diseases models. The eye, brain, and tumor tissues are 'hot' target tissues/organs for local siRNA delivery. The siRNA can be delivered locally, in naked form, with chemical modifications, or in formulations with viral or non-viral vectors, such as liposomes and nanoparticles. This review provides a comprehensive overview of RNAi local administration and potential future applications in clinical treatment.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, Shaanxi; State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, Shaanxi, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: He
authors.affiliation: School of Stomatology, Central South University, Changsha 410078, Hunan, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, Shaanxi, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
mesh_terms: D000287:Administration, Topical; D005822:Genetic Vectors; D006801:Humans; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D034741:RNA, Small Interfering
references.citation: Cell. 2012 Aug 31;150(5):895-908
references.pmid: 22939619
references.citation: Nat Biotechnol. 2009 Sep;27(9):839-49
references.pmid: 19701187
references.citation: Cell. 2012 Aug 31;150(5):883-94
references.pmid: 22939618
references.citation: J Control Release. 2014 Jan 10;173:110-8
references.pmid: 24120854
references.citation: Adv Drug Deliv Rev. 2010 Apr 30;62(6):650-66
references.pmid: 20230868
references.citation: Mol Ther. 2014 Jan;22(1):226-32
references.pmid: 24025752
references.citation: Nature. 2006 May 4;441(7089):111-4
references.pmid: 16565705
references.citation: Biomaterials. 2014 Mar;35(9):2905-14
references.pmid: 24397988
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17204-9
references.pmid: 17940007
references.citation: Mol Ther. 2014 Jan;22(1):81-91
references.pmid: 24025749
references.citation: J Control Release. 2014 Mar 28;178:18-24
references.pmid: 24440662
references.citation: Nature. 2001 May 24;411(6836):494-8
references.pmid: 11373684
references.citation: ACS Nano. 2012 Jun 26;6(6):4835-44
references.pmid: 22621383
references.citation: Cell Death Dis. 2011 Jun 16;2:e173
references.pmid: 21677688
references.citation: Sci Transl Med. 2014 Jan 1;6(217):217ra2
references.pmid: 24382894
references.citation: Nature. 1998 Feb 19;391(6669):806-11
references.pmid: 9486653
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14993-8
references.pmid: 18820032
references.citation: J Control Release. 2014 Mar 28;178:79-85
references.pmid: 24462901
references.citation: Hum Gene Ther. 2008 Feb;19(2):125-32
references.pmid: 18257677