Double-stranded and single-stranded RNA molecules with 5 ' triphosphates and their use for inducing interferon

Abstract

Double-stranded and single-stranded RNA molecules, and their use in methods for inducing interferon are provided. The interferon induction provides anti-viral and other medically useful effects, such as anti-cancer effects. Also provided are methods for reducing or inhibiting interferon induction exhibited by such molecules, particularly siRNA and shRNA molecules produced in vitro.

Description

CROSS-REFERNCE TO RELATED APPLICATION [0001] The present application is related to and claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application Ser. No. 60 / 649,537 filed on 4 Feb. 2005, incorporated herein by reference.[0002] The invention described herein was made with Government support under grant number HL074704 from NHLBI of the National Institutes of Health. Accordingly, the United States Government may have certain rights in this invention.FIELD OF THE INVENTION [0003] The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference, and for convenience are referenced in the following text by author and date and are listed alphabetically by author in the appended bibliography. [0004] The present invention relates to RNA molecules, including double-stranded and single-stranded RNA molecules, and their use for induci...

AI Technical Summary

Benefits of technology

[0011] The present invention is believed to be first to show that the presence of an initiating triphosphate on in vitro transcribed-RNAs can potently induce interferon α and β, as well as elicit a strong, non-sequence-specific antiviral response to viral challenge.

[0013] The present invention relates in one embodiment to a method for inducing interferon in a cell, comprising exposing or introducing into the cell an effective amount of an RNAi molecule having one or more triphosphates, preferably a 5′-triphosphate, wherein said RNAi molecule induces said interferon. The RNAi molecule also can have an anti-viral effect, and preferably, is introduced into the cell prior to viral infection, wherein the RNAi molecule inhibits or prevents viral infection. The RNAi molecule also can have other medically useful effects, such as an anti-cancer effect.

[0014] In another embodiment, the invention provides a composition for inducing interferon in a cell comprising an effective amount of an RNAi molecule having one or more triphosphates, preferably a 5′-triphosphate, wherein the RNAi molecule can induce interferon in the cell. In a preferred embodiment, the RNAi molecule can also have an anti-viral or anti-cancer effect.

Problems solved by technology

However, when synthetic siRNAs are used for gene silencing, the costs can be substantial because of variations in siRNA efficacies.

Although the anti-viral activities of interferons are well studied (Samuel, C. E., 2001), nobody has recognized in connection with RNAi the uses and advantages, as opposed to the risks, of interferon induction by RNAi molecules, independent of the RNAi effect, to provide anti-viral and other effects, such as anti-cancer effects.

Moreover, until now, nobody is believed to have discovered the role of the triphosphate, in particular the 5-triphosphate produced on RNAi molecules in vitro, for inducing interferon and eliciting anti-viral and other medically useful responses.

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