Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC.

Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Research Abstract Details 

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Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Abstract Text:

Daniela Castanotto,Kumi Sakurai,Robert Lingeman,Haitang Li,Louise Shively,Lars Aagaard,Harris Soifer,Anne Gatignol,Arthur Riggs,John J Rossi,

Despite the great potential of RNAi, ectopic expression of shRNA or siRNAs holds the inherent risk of competition for critical RNAi components, thus altering the regulatory functions of some cellular microRNAs. In addition, specific siRNA sequences can potentially hinder incorporation of other siRNAs when used in a combinatorial approach. We show that both synthetic siRNAs and expressed shRNAs compete against each other and with the endogenous microRNAs for transport and for incorporation into the RNA induced silencing complex (RISC). The same siRNA sequences do not display competition when expressed from a microRNA backbone. We also show that TAR RNA binding protein (TRBP) is one of the sensors for selection and incorporation of the guide sequence of interfering RNAs. These findings reveal that combinatorial siRNA approaches can be problematic and have important implications for the methodology of expression and use of therapeutic interfering RNAs.

Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Publishing Authors By Initials

D Castanotto,K Sakurai,R Lingeman,H Li,L Shively,L Aagaard,H Soifer,A Gatignol,A Riggs,JJ Rossi,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Nucleic acids research

VOLUME: 35

Page Numbers: 5154-64

Journal Abbreviation: Nucleic Acids Res.

ISSN: 1362-4962

DAY: 26

MONTH: 07

YEAR: 2007

Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 411011

Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC. Information

Substance Name: trans-activation responsive RNA-binding

Registry Number: 136628-24-5

Grant and Affiliation Information for Combinatorial delivery of small interfering RNAs reduces RNAi efficacy by selective incorporation into RISC.

AFFILIATION: Division of Molecular Biology, Beckman Research Institute of the City of Hope, USA.

Country: England

AGENCY: United States NHLBI

GRANT: HL07470

ACRONYM: HL

MEDLINETA: Nucleic Acids Res

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