Towards in vivo application of RNA interference – new toys, old problems 英文参考文献.docVIP

Arthritis Research Therapy Vol 6 No 2 Rutz and Scheffold Technology review Towards in vivo application of RNA interference – new toys, old problems Sascha Rutz and Alexander Scheffold Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany Corresponding author: Alexander Scheffold (e-mail: scheffold@drfz.de) Received: 17 Dec 2003 Revisions requested: 11 Feb 2004 Revisions received: 25 Feb 2004 Accepted: 26 Feb 2004 Published: 10 Mar 2004 Arthritis Res Ther 2004, 6:78-85 (DOI 10.1186/ar1168) ? 2004 BioMed Central Ltd (Print ISSN 1478-6354; Online ISSN 1478-6362) Abstract RNA interference (RNAi) is the sequence-specific degradation of mRNA by short double-stranded RNA molecules. The technology, introduced only 5 years ago, has stimulated many fantasies regarding the future of functional gene analysis and gene therapy. Given its ease of application, its high efficiency and remarkable specificity, RNAi holds great promise for broad in vitro and in vivo application in all areas of biomedicine. Despite its potential, the major obstacle to the use of RNAi (as for all previous gene silencing approaches) is the need for efficient and sustained delivery of small interfering RNA into primary mammalian cells, and specific targeting of particular cell types in vivo. Keywords: functional genomics, gene silencing, primary mammalian cell, small interfering RNA, transfection Introduction to defend against invading nucleic acids such as viruses and transposons [2,3], and therefore it is easily applicable to a large variety of organisms, cell types and genes. The technology has remarkable target specificity and requires only low amounts of siRNA effector molecules per cell, which can even be expressed directly in situ, allowing long-term silencing of target genes. This makes RNAi an interesting tool for the analysis of loss-of-function pheno- types in vivo and it may also lead to the development of ne