Immunosuppression compound and treatment method

摘要

A method and compound for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection are disclosed. The compound is an antisense oligonucleotide analog compound having a targeting sequence complementary to a preprocessed CTLA-4 mRNA region identified by SEQ ID NO: 22 in SEQ ID NO: 1, spanning the splice junction between intron 1 and exon 2 of the preprocessed mRNA of the subject. The compound is 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.

主权项

1. A phosphorodiamidate morpholino antisense oligonucleotide of 12 to 40 bases comprising a base sequence that is 100% complementary to contiguous bases of human CTLA-4 pre-mRNA, wherein the base sequence comprises at least 12 contiguous bases that are 100 complementary to SEQ ID NO: 22, and wherein the phosphorodiamidate morpholino antisense oligonucleotide induces skipping of exon 2 of the human CTLA-4 pre-mRNA.