Arabinonucleic Acids: 2′-Stereoisomeric Modulators of siRNA Activity

被引：9

作者：

Anzahaee, Maryam Yahyaee ^{[1
]}

Deleavey, Glen F. ^{[1
]}

Phuong Uyen Le ^{[2
]}

Fakhoury, Johans ^{[1
]}

Petrecca, Kevin ^{[2
]}

Damha, Masad J. ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada

[2] McGill Univ, Montreal Neurol Inst & Hosp, Dept Neurol & Neurosurg, Brain Tumour Res Ctr, Montreal, PQ H3A 2K6, Canada

来源：

NUCLEIC ACID THERAPEUTICS | 2014年 / 24卷 / 05期

关键词：

CONTROLLED INTRACELLULAR-LOCALIZATION; RNA INTERFERENCE; MODIFIED OLIGONUCLEOTIDES; MAMMALIAN-CELLS; HYBRID DUPLEXES; RIBONUCLEASE H; IN-VIVO; GENE; 2'F-ANA; DELIVERY;

D O I：

10.1089/nat.2014.0496

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have investigated, for the first time, short interfering duplexes containing arabinonucleotides (ANA; the 2'-stereoisomer of RNA), as well as combinations of ANA with RNA, and their 2'-fluorinated derivatives 2F-ANA and/or 2'F-RNA. The results show that ANA is especially well accommodated in the sense strand of small interfering RNA (siRNA) duplexes, which can be extensively modified with little effect on potency. Furthermore, combining ANA with RNA and 2'F-ANA in siRNA passenger strands, particularly in patterns that bias duplex thermal stability, produces duplexes with similar (and sometimes enhanced) potency compared with native siRNA. Effective patterns of modification were identified against firefly luciferase screens in HeLa cells and then applied to knockdown of down-regulated in renal cell carcinoma (DRR), a novel and clinically tractable target for the treatment of glioblastoma.

引用

页码：336 / 343

页数：8

共 51 条

[1] Tolerance for mutations and chemical modifications in a siRNA [J].

Amarzguioui, M ;

Holen, T ;

Babaie, E ;

Prydz, H .

NUCLEIC ACIDS RESEARCH, 2003, 31 (02) :589-595

[2]

Bellon L., 2001, CURRENT PROTOCOLS NU, V1

[3] Fully 2′-Deoxy-2′-Fluoro substituted nucleic acids induce RNA interference in mammalian cell culture [J].

Blidner, Richard A. ;

Hammer, Robert P. ;

Lopez, Mandi J. ;

Robinson, Sandra O. ;

Monroe, W. Todd .

CHEMICAL BIOLOGY & DRUG DESIGN, 2007, 70 (02) :113-122

[4] RNA interference in mammalian cells by chemically-modified RNA [J].

Braasch, DA ;

Jensen, S ;

Liu, YH ;

Kaur, K ;

Arar, K ;

White, MA ;

Corey, DR .

BIOCHEMISTRY, 2003, 42 (26) :7967-7975

[5] Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells [J].

Czauderna, F ;

Fechtner, M ;

Dames, S ;

Aygün, H ;

Klippel, A ;

Pronk, GJ ;

Giese, K ;

Kaufmann, J .

NUCLEIC ACIDS RESEARCH, 2003, 31 (11) :2705-2716

[6] Hybrids of RNA and arabinonucleic acids (ANA and 2′F-ANA) are substrates of ribonuclease h [J].

Damha, MJ ;

Wilds, CJ ;

Noronha, A ;

Brukner, I ;

Borkow, G ;

Arion, D ;

Parniak, MA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (49) :12976-12977

[7]

Deleavey GF, 2010, CURRENT PROTOCOLS NU, V1, P16

[8] The 5′ Binding MID Domain of Human Argonaute2 Tolerates Chemically Modified Nucleotide Analogues [J].

Deleavey, Glen F. ;

Frank, Filipp ;

Hassler, Matthew ;

Wisnovsky, Simon ;

Nagar, Bhushan ;

Damha, Masad J. .

NUCLEIC ACID THERAPEUTICS, 2013, 23 (01) :81-87

[9] Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing [J].

Deleavey, Glen F. ;

Damha, Masad J. .

CHEMISTRY & BIOLOGY, 2012, 19 (08) :937-954

[10] Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing [J].

Deleavey, Glen F. ;

Watts, Jonathan K. ;

Alain, Tommy ;

Robert, Francis ;

Kalota, Anna ;

Aishwarya, Veenu ;

Pelletier, Jerry ;

Gewirtz, Alan M. ;

Sonenberg, Nahum ;

Damha, Masad J. .

NUCLEIC ACIDS RESEARCH, 2010, 38 (13) :4547-4557

← 1 2 3 4 5 6 →