5'-Morpholino modification of the sense strand of an siRNA makes it a more effective passenger

Pawan Kumar; Rubina G Parmar; Christopher R Brown; Jennifer L S Willoughby; Donald J Foster; I Ramesh Babu; Sally Schofield; Vasant Jadhav; Klaus Charisse; Jayaprakash K Nair; Kallanthottathil G Rajeev; Martin A Maier; Martin Egli; Muthiah Manoharan

doi:10.1039/c9cc00977a

5'-Morpholino modification of the sense strand of an siRNA makes it a more effective passenger

Chem Commun (Camb). 2019 Apr 25;55(35):5139-5142. doi: 10.1039/c9cc00977a.

Authors

Pawan Kumar¹, Rubina G Parmar, Christopher R Brown, Jennifer L S Willoughby, Donald J Foster, I Ramesh Babu, Sally Schofield, Vasant Jadhav, Klaus Charisse, Jayaprakash K Nair, Kallanthottathil G Rajeev, Martin A Maier, Martin Egli, Muthiah Manoharan

Affiliation

¹ Alnylam Pharmaceuticals, 300 Third Street, Cambridge, Massachusetts 02142, USA. [email protected].

PMID: 30977478
DOI: 10.1039/c9cc00977a

Abstract

The 5'-monophosphate group plays an important role in strand selection during gene silencing mediated by small-interfering RNA. We show that blocking of 5' phosphorylation of the sense strand by introducing a 5'-morpholino modification improves antisense strand selection and RNAi activity. The 5'-morpholino modification of the antisense strand triggers complete loss of activity.

MeSH terms

Animals
Apolipoprotein B-100
Apolipoproteins B / genetics
Argonaute Proteins / genetics
Gene Silencing
Humans
Mice
Models, Molecular
Morpholinos / chemical synthesis
Morpholinos / chemistry*
Morpholinos / genetics
RNA Interference
RNA, Small Interfering / chemical synthesis
RNA, Small Interfering / chemistry*
RNA, Small Interfering / genetics

Substances

Ago2 protein, mouse
Apob protein, mouse
Apolipoprotein B-100
Apolipoproteins B
Argonaute Proteins
Morpholinos
RNA, Small Interfering