Antisense oligomers and methods for inducing immune tolerance and immunosuppression
First Claim
1. A method of inducing increased production of extracellular IL-10 in mature dendritic cells, comprising(a) exposing a population of human dendritic cells that includes mature dendritic cells to an antisense compound composed of phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit and containing 12-40 subunits, including a base sequence of at least 12 contiguous bases that are complementary to a target region within the sequence identified by SEQ ID NO;
9, wherein said compound is covalently linked, at one compound end, to an arginine-rich peptide effective to enhance uptake of said compound into the mature dendritic cells, and(b) by said exposing in step (a), blocking expression of full-length CD86 in said cells,(c) by said blocking, thereby producing inhibition of the expression of full-length CD86 on the surface of mature dendritic cells, and enhanced expression of extracellular IL-10 by mature dendritic cells.
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Abstract
A method and composition for inducing human dendritic cells to a condition of reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10 is disclosed. A population of dendritic cells is exposed to a substantially uncharged antisense compound, including partially positively charged, containing 12-40 subunits and a base sequence effective to hybridize to a target region within the sequence identified by SEQ ID NO:9, to form a duplex structure between the compound and transcript having a Tm of at least 45° C. Formation of the duplex blocks expression of full-length CD86 in the cells, which in turn leads to reduced capacity for antigen-specific activation of T cells, and, in mature dendritic cells, increased production of extracellular IL-10.
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Citations
14 Claims
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1. A method of inducing increased production of extracellular IL-10 in mature dendritic cells, comprising
(a) exposing a population of human dendritic cells that includes mature dendritic cells to an antisense compound composed of phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ - exocyclic carbon of an adjacent subunit and containing 12-40 subunits, including a base sequence of at least 12 contiguous bases that are complementary to a target region within the sequence identified by SEQ ID NO;
9, wherein said compound is covalently linked, at one compound end, to an arginine-rich peptide effective to enhance uptake of said compound into the mature dendritic cells, and(b) by said exposing in step (a), blocking expression of full-length CD86 in said cells, (c) by said blocking, thereby producing inhibition of the expression of full-length CD86 on the surface of mature dendritic cells, and enhanced expression of extracellular IL-10 by mature dendritic cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
- exocyclic carbon of an adjacent subunit and containing 12-40 subunits, including a base sequence of at least 12 contiguous bases that are complementary to a target region within the sequence identified by SEQ ID NO;
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14. A method of inducing mature human dendritic cells to a condition of increased production of extracellular IL-10, comprising
(a) exposing a population of human dendritic cells that comprises mature dendritic cells to an antisense compound composed of phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ - exocyclic carbon of an adjacent subunit and containing 12-40 subunits, including a base sequence of at least 12 contiguous bases that are complementary to a target region within the sequence identified by SEQ ID NO;
9, wherein said compound is covalently linked to an arginine-rich rTAT peptide having the sequence identified by SEQ ID NO;
1, and(b) by said exposing in step (a), blocking expression of full-length CD86 in said cells, (c) thereby enhancing expression of extracellular IL-10 by the mature dendritic cells.
- exocyclic carbon of an adjacent subunit and containing 12-40 subunits, including a base sequence of at least 12 contiguous bases that are complementary to a target region within the sequence identified by SEQ ID NO;
Specification