Methods and compositions for therapeutic use of rna interference
AssigneeInsert Therapeutics, Inc.
InventorsMark E. Davis, Gregory S. Jensen, Suzie Hwang Pun
Life of this patent
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Abstract
Abstract of Disclosure The present invention provides methods and compositions for attenuating expression of a target gene in vivo. In general, the method includes administering RNAi constructs (such as small-interfering RNAs (i.e., siRNAs) that are targeted to particular mRNA sequences, or nucleic acid material that can produce siRNAs in a cell), in an amount sufficient to attenuate expression of a target gene by an RNA interference mechanism, e.g., in a sequence-dependent, PKR-independent manner. In particular, the subject method can be used to alter the growth, survival or differentiation of cells for therapeutic and cosmetic purposes.
Claims212
A stable respiratory formulation comprising RNAi constructs formulated for pulmonary or nasal delivery of a therapeutically effective amount of said RNAi constructs to the lungs of a patient.
A metered dose aerosol dispenser containing an aerosol pharmaceutical composition for pulmonary or nasal delivery comprising a respirable formulation of RNAi constructs.
A method for affecting systemic administration of an RNAi construct comprising administering to a patient, by way of pulmonary administration, a respirable formulation of RNAi constructs which is taken up in an amount in the deep lung to deliver a systemic dose of said RNAi construct.
A composition comprising one or more RNAi constructs formulated in a supramolecular complex and in an amount sufficient to attenuate expression of a target gene in treated cells through an RNA interference mechanism.
A method for attenuating expression of a target gene of a cell in vivo, comprising administering an RNAi construct, formulated in a supramolecular complex, in an amount sufficient to attenuate expression of the target gene through an RNA interference mechanism, and thereby alter the growth, survival or differentiation of treated cells.
A coating for use on a surface of a medical device, comprising a polymer matrix having RNAi constructs dispersed therein, which RNAi constructs are eluted from the matrix when implanted at site in a patient"s body and alter the growth, survival or differentiation of cells in the vicinity of the implanted device.
A method for coating a medical device with one or more RNAi constructs, comprising:
- a) formulating the RNAi construct for coating a surface of a device such that said RNAi constructs are eluted from the surface when the device is implanted at site in a patient"s body;
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- b) coating the formulated RNAi construct on a medical device, wherein the medical device coated with the RNAi construct attenuates expression of one or more genes in cells in the vicinity of the implanted device.
A composition comprising one or more RNAi constructs formulated for percutaneous intrapericardial delivery to an animal.
A method for percutaneous intrapericardial delivery of one or more RNAi constructs in vivo, comprising administering a formulation of RNAi constructs to the pericardial space of an animal, wherein the RNAi constructs are present in an amount sufficient to attenuate expression of one or more target genes of cells of the treated animal.
A composition comprising one or more RNAi constructs formulated in liposomes for attenuating expression of a target gene of cells in vivo through an RNA interference mechanism.
A method for attenuating expression of a target gene of cells of a patient, comprising administering RNAi constructs formulated in liposomes and in an amount sufficient to attenuate expression of a target gene through an RNA interference mechanism, so as to thereby alter the growth, survival or differentiation of said cells.
A composition comprising one or more RNAi constructs formulated for electroporation into cells in vivo.
A method for delivering one or more RNAi constructs to a patient by electroporation, comprising administering the RNAi construct of sufficient amount to an animal through electroporation, wherein the RNAi construct attenuates expression of a target gene in cells of the patient.
A composition comprising one or more formulated RNAi constructs for inhibiting unwanted cell growth in vivo, wherein, through an RNA interference mechanism, the RNAi construct reduces expression of a target gene essential to mitosis of a cell and/or which is essential to preventing apoptosis of said cell.
A method for inhibiting unwanted cell growth in vivo, comprising administering to an animal a formulated RNAi construct of sufficient amount, wherein, through an RNA interference mechanism, the RNAi construct reduces expression of a target gene essential to mitosis of a cell and/or which is essential to preventing apoptosis of said cell.
A pharmaceutical package comprising the pharmaceutical preparation of claim195, in association with instructions for administering the preparation to a human patient.
A method for inducing cell death, comprising administering to target cells in vivo an double stranded RNA, or an expression vector capable of transcribing a double stranded RNA, of sufficient length to activate a PKR response in the target cells, which double stranded RNA is formulated as part of a supramolecular complex.
The method of claim199, wherein the double stranded RNA is more than 35 basepairs in length.
The method of claim199, wherein the target cells are mammalian cells.
The method of claim199, wherein the target cells are transformed cells.
A method of conducting a pharmaceutical business comprising:
- a). identifying an RNAi construct which inhibits proliferation of target cells in vivo and reduces the effects of a disorder involving unwanted proliferation of the target cells;
- b). conducting therapeutic profiling of the RNAi construct identified in step (a) for efficacy and toxicity in animals;
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- c). formulating a pharmaceutical preparation including one or more RNAi constructs identified in step (b) as having an acceptable therapeutic profile.
A method of conducting a pharmaceutical business comprising:
- a). identifying an RNAi construct which inhibits proliferation of target cells in vivo and reduces the effects of a disorder involving unwanted proliferation of the target cells;
- b). (optionally) conducting therapeutic profiling of the RNAi construct identified in step (a) for efficacy and toxicity in animals;
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- c). licensing, to a third party, the rights for further development of the RNAi construct.
Dependencies are inferred from the claim text.