Genetic inhibition by double-stranded RNA

Abstract

A process is provided of introducing an RNA into a living cell to inhibit gene expression of a target gene in that cell. The process may be practiced ex vivo or in vivo. The RNA has a region with double-stranded structure. Inhibition is sequence-specific in that the nucleotide sequences of the duplex region of the RNA and of a portion of the target gene are identical. The present invention is distinguished from prior art interference in gene expression by antisense or triple-strand methods.

Description

RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Appln. No. 60 / 068,562, filed Dec. 23, 1997.GOVERNMENT RIGHTS

[0002] This invention was made with U.S. government support under grant numbers GM-37706, GM-17164, HD-33769 and GM-07231 awarded by the National Institutes of Health. The U.S. government has certain rights in the invention.BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates to gene-specific inhibition of gene expression by double-stranded ribonucleic acid (dsRNA).

[0005] 2. Description of the Related Art

[0006] Targeted inhibition of gene expression has been a long-felt need in biotechnology and genetic engineering. Although a major investment of effort has been made to achieve this goal, a more comprehensive solution to this problem was still needed.

[0007] Classical genetic techniques have been used to isolate mutant organisms with reduced expression of selected genes. Although valuable, such ...

Examples

Embodiment Construction

[0028] The present invention provides a method of producing sequence-specific inhibition of gene expression by introducing double-stranded RNA (dsRNA). A process is provided for inhibiting expression of a target gene in a cell. The process comprises introduction of RNA with partial or fully double-stranded character into the cell. Inhibition is sequence-specific in that a nucleotide sequence from a portion of the target gene is chosen to produce inhibitory RNA. We disclose that this process is (1) effective in producing inhibition of gene expression, (2) specific to the targeted gene, and (3) general in allowing inhibition of many different types of target gene.

[0029] The target gene may be a gene derived from the cell (i.e., a cellular gene), an endogenous gene (i.e., a cellular gene present in the genome), a transgene (i.e., a gene construct inserted at an ectopic site in the genome of the cell), or a gene from a pathogen which is capable of infecting an organism from which the c...

RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Appln. No. 60 / 068,562, filed Dec. 23, 1997.GOVERNMENT RIGHTS

[0002] This invention was made with U.S. government support under grant numbers GM-37706, GM-17164, HD-33769 and GM-07231 awarded by the National Institutes of Health. The U.S. government has certain rights in the invention.BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates to gene-specific inhibition of gene expression by double-stranded ribonucleic acid (dsRNA).

[0005] 2. Description of the Related Art

[0006] Targeted inhibition of gene expression has been a long-felt need in biotechnology and genetic engineering. Although a major investment of effort has been made to achieve this goal, a more comprehensive solution to this problem was still needed.

[0007] Classical genetic techniques have been used to isolate mutant organisms with reduced expression of selected genes. Although valuable, such ...

Examples

Embodiment Construction

[0028] The present invention provides a method of producing sequence-specific inhibition of gene expression by introducing double-stranded RNA (dsRNA). A process is provided for inhibiting expression of a target gene in a cell. The process comprises introduction of RNA with partial or fully double-stranded character into the cell. Inhibition is sequence-specific in that a nucleotide sequence from a portion of the target gene is chosen to produce inhibitory RNA. We disclose that this process is (1) effective in producing inhibition of gene expression, (2) specific to the targeted gene, and (3) general in allowing inhibition of many different types of target gene.

[0029] The target gene may be a gene derived from the cell (i.e., a cellular gene), an endogenous gene (i.e., a cellular gene present in the genome), a transgene (i.e., a gene construct inserted at an ectopic site in the genome of the cell), or a gene from a pathogen which is capable of infecting an organism from which the c...

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