| 摘要 |
Provided are methods and antisense oligonucleotide analogs for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection. The oligonucleotide analogs provided herein comprise a targeting sequence complementary to a preprocessed CTLA-4 mRNA region that spans the splice junction between intron 1 and exon 2 of the preprocessed CTLA-4 mRNA. Also provided are methods of use, in which the oligonucleotides are effective, when administered to a subject, to form within host cells, a heteroduplex structure (i) composed of the preprocessed CTLA-4 mRNA and the oligonucleotide compound, (ii) characterized by a Tm of dissociation of at least 45° C., and (iii) resulting in an increased ratio of processed mRNA encoding ligand-independent CTLA-4 to processed mRNA encoding full-length CTLA-4.
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