Biodistribution of phosphodiester and phosphorothioate siRNA

Dwaine A. Braasch; Zain Paroo; Anca Constantinescu; Gang Ren; Orhan K. Öz; Ralph P. Mason; David R. Corey

doi:10.1016/j.bmcl.2003.12.074

Biodistribution of phosphodiester and phosphorothioate siRNA

Dwaine A. Braasch, Zain Paroo, Anca Constantinescu, Gang Ren, Orhan K. Öz, Ralph P. Mason, David R. Corey

Research output: Contribution to journal › Article › peer-review

237 Scopus citations

Abstract

Short interfering RNAs (siRNAs) are valuable tools for analyzing protein function in mammalian cell culture. This success has led to high expectations for in vivo and therapeutic applications. However, the pharmacokinetic properties of siRNA are not known. Here we report the biodistribution of a phosphodiester (PO) siRNA duplex and examine the effect of phosphorothioate (PS) linkages. Our findings indicate that biodistribution of siRNA is similar to that for single-stranded antisense oligonucleotides and offer insights for use of siRNA in vivo.

Original language	English (US)
Pages (from-to)	1139-1143
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2003.12.074
State	Published - Mar 8 2004

Keywords

Biodistribution
Phosphorothioate
Planar imaging
siRNA

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2003.12.074

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title = "Biodistribution of phosphodiester and phosphorothioate siRNA",

abstract = "Short interfering RNAs (siRNAs) are valuable tools for analyzing protein function in mammalian cell culture. This success has led to high expectations for in vivo and therapeutic applications. However, the pharmacokinetic properties of siRNA are not known. Here we report the biodistribution of a phosphodiester (PO) siRNA duplex and examine the effect of phosphorothioate (PS) linkages. Our findings indicate that biodistribution of siRNA is similar to that for single-stranded antisense oligonucleotides and offer insights for use of siRNA in vivo.",

keywords = "Biodistribution, Phosphorothioate, Planar imaging, siRNA",

author = "Braasch, {Dwaine A.} and Zain Paroo and Anca Constantinescu and Gang Ren and {\"O}z, {Orhan K.} and Mason, {Ralph P.} and Corey, {David R.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (GM60642 to D.R.C., CA096354 to R.P.M., and HD01463 to O.K.O.) and the Robert A. Welch Foundation (I-1244 to D.R.C.).",

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language = "English (US)",

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AU - Braasch, Dwaine A.

AU - Paroo, Zain

AU - Constantinescu, Anca

AU - Ren, Gang

AU - Öz, Orhan K.

AU - Mason, Ralph P.

AU - Corey, David R.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (GM60642 to D.R.C., CA096354 to R.P.M., and HD01463 to O.K.O.) and the Robert A. Welch Foundation (I-1244 to D.R.C.).

PY - 2004/3/8

Y1 - 2004/3/8

N2 - Short interfering RNAs (siRNAs) are valuable tools for analyzing protein function in mammalian cell culture. This success has led to high expectations for in vivo and therapeutic applications. However, the pharmacokinetic properties of siRNA are not known. Here we report the biodistribution of a phosphodiester (PO) siRNA duplex and examine the effect of phosphorothioate (PS) linkages. Our findings indicate that biodistribution of siRNA is similar to that for single-stranded antisense oligonucleotides and offer insights for use of siRNA in vivo.

AB - Short interfering RNAs (siRNAs) are valuable tools for analyzing protein function in mammalian cell culture. This success has led to high expectations for in vivo and therapeutic applications. However, the pharmacokinetic properties of siRNA are not known. Here we report the biodistribution of a phosphodiester (PO) siRNA duplex and examine the effect of phosphorothioate (PS) linkages. Our findings indicate that biodistribution of siRNA is similar to that for single-stranded antisense oligonucleotides and offer insights for use of siRNA in vivo.

KW - Biodistribution

KW - Phosphorothioate

KW - Planar imaging

KW - siRNA

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Biodistribution of phosphodiester and phosphorothioate siRNA

Abstract

Keywords

ASJC Scopus subject areas

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