Chemically modified oligonucleotides targeting bromodomain containing protein 4 (BRD4) for immunotherapy
AssigneePhio Pharmaceuticals Corp.
InventorsJames Cardia, Rolf Kiessling, Jeroen Melief
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Abstract
The disclosure relates, in some aspects, to methods and compositions for production of immunomodulatory compositions. In some embodiments, the disclosure provides host cells which have been treated ex vivo with one or more oligonucleotide agents capable of controlling and/or reducing the differentiation of the host cell. In some embodiments, compositions and methods described by the disclosure are useful as immunogenic modulators for treating cancer.
Claims16
An isolated asymmetric double stranded nucleic acid molecule comprising a guide strand, with a minimal length of 16 nucleotides, and a passenger strand of 8-18 nucleotides in length, wherein the double stranded nucleic acid molecule has a double stranded region and a single stranded region, the single stranded region having 4-12 nucleotides in length and having at least three nucleotide backbone modifications, wherein the isolated asymmetric double stranded nucleic acid molecule is directed against a gene encoding BRD4, and wherein the sequence of the isolated asymmetric double stranded nucleic acid molecule comprises at least 12 contiguous nucleotides of:
- SEQ ID NO:
- 87 (fG.mA.fU.mG.fU.mG.fU.mU.fC.mG.fA.mA.fA*mU*fA.TEG-Chl) and/or
- SEQ ID NO:
- 88 (P.mU.fA.mU.fU.mU.fC.mG.fA.mA.fC.mA.fC.mA.fU*mC*fC*mU*fG*mG*fA).
An immunomodulatory composition comprising a host cell which was treated ex vivo with a chemically-modified double stranded nucleic acid molecule that is directed against a gene encoding BRD4 to control and/or reduce the level of differentiation of the host cell to enable the production of a specific immune cellular population for administration in a human, wherein the sequence of the chemically-modified double stranded nucleic acid molecule comprises at least 12 contiguous nucleotides of:
- SEQ ID NO:
- 87 (fG.mA.fU.mG.fU.mG.fU.mU.fC.mG.fA.mA.fA*mU*fA.TEG-Chl) and/or
- SEQ ID NO:
- 88 (P.mU.fA.mU.fU.mU.fC.mG.fA.mA.fC.mA.fC.mA.fU*mC*fC*mU*fG*mG*fA).
Dependencies are inferred from the claim text.