Shorter Is Better: The α-(l)-Threofuranosyl Nucleic Acid Modification Improves Stability, Potency, Safety, and Ago2 Binding and Mitigates Off-Target Effects of Small Interfering RNAs.

Animals Mice Rats RNA, Small Interfering Nucleic Acids Nucleotides RNA Interference Acetylgalactosamine

Journal

Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056

Informations de publication

Date de publication:
13 09 2023
Historique:
medline: 14 9 2023
pubmed: 28 8 2023
entrez: 28 8 2023
Statut: ppublish

Résumé

Chemical modifications are necessary to ensure the metabolic stability and efficacy of oligonucleotide-based therapeutics. Here, we describe analyses of the α-(l)-threofuranosyl nucleic acid (TNA) modification, which has a shorter 3'-2' internucleotide linkage than the natural DNA and RNA, in the context of small interfering RNAs (siRNAs). The TNA modification enhanced nuclease resistance more than 2'-

Identifiants

DOI: 10.1021/jacs.3c04744 PMID: 37638886
pubmed: 37638886
doi: 10.1021/jacs.3c04744
doi:

Substances chimiques

RNA, Small Interfering 0
Nucleic Acids 0
Nucleotides 0
Acetylgalactosamine KM15WK8O5T

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

19691-19706

Auteurs

Shigeo Matsuda (S)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Saikat Bala (S)

Department of Pharmaceutical Sciences, University of California, Irvine, California 92697-3958, United States.
ORCID: 0000-0002-5285-4476

Jen-Yu Liao (JY)

Department of Pharmaceutical Sciences, University of California, Irvine, California 92697-3958, United States.

Dhrubajyoti Datta (D)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Atsushi Mikami (A)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Lauren Woods (L)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Joel M Harp (JM)

Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-0146, United States.

Jason A Gilbert (JA)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Anna Bisbe (A)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Rajar M Manoharan (RM)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

MaryBeth Kim (M)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Christopher S Theile (CS)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Dale C Guenther (DC)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Yongfeng Jiang (Y)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Saket Agarwal (S)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.
ORCID: 0000-0002-1681-2842

Rajanikanth Maganti (R)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Mark K Schlegel (MK)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.
ORCID: 0000-0002-0127-608X

Ivan Zlatev (I)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Klaus Charisse (K)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Kallanthottathil G Rajeev (KG)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Adam Castoreno (A)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Martin Maier (M)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Maja M Janas (MM)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Martin Egli (M)

Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-0146, United States.
ORCID: 0000-0003-4145-356X

John C Chaput (JC)

Department of Pharmaceutical Sciences, University of California, Irvine, California 92697-3958, United States.
ORCID: 0000-0003-1393-135X

Muthiah Manoharan (M)

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.
ORCID: 0000-0002-7931-1172

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Interférence par ARN › Shorter Is Better: The α-(l)-Threofuranosyl...
questionsmedicales.fr › Glucides › Osamines › Hexosamine › Galactosamine › Acétyl-galactosamine › Shorter Is Better: The α-(l)-Threofuranosyl...