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†

Pawan Kumar,

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

^b and Muthiah Manoharan

*^a

Author affiliations

* Corresponding authors

^a Alnylam Pharmaceuticals, 300 Third Street, Cambridge, Massachusetts 02142, USA
E-mail: mmanoharan@alnylam.com

^b Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232-0146, USA

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.

Chemical Communications

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

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

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