TARGETED DELIVERY TO LEUKOCYTES USING NON-PROTEIN CARRIERS
申请公布号:US2010008937(A1)
申请号:US20070298367
申请日期:2007.04.25
申请公布日期:2010.01.14
发明人:PEER DAN;SHIMAOKA MOTOMU
分类号:A61K47/48;A61K9/127;A61K35/00;A61K38/02;A61K39/395;C07H21/02;C07K2/00;C12N5/00;C12N15/11;C12N15/113;C12N15/87
主分类号:A61K47/48
摘要:Disclosed are delivery agents for selective delivery to leukocytes. The leukocyte-selective delivery agents comprise a targeting moiety that selectively binds LFA-I, a non-protein carrier moiety covalently linked to the targeting moiety and a therapeutic agent associated with the carrier moiety. The non-protein carrier moiety comprises a liposome, a micelle, or a polymeric nanoparticle comprised of PLA or PLGA. The delivery agent may be further selective for activated leukocytes by using a targeting moiety that selectively binds LFA-I in its activated conformation. The targeting moiety may comprise an antibody or functional fragment thereof such as an scFV. Appropriate therapeutic agents include a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. Additional examples of therapeutic agents are a small RNA, an antagomir, an LNA, or an antisense oligonucleotide. One such therapeutic agent is an RNA interference molecule such as siRNA, dsRNA, stRNA, shRNA, miRNA. Specific delivery agents are provided. Methods for in vivo, in vitro and ex vivo leukocyte-selective delivery using the delivery agents are also disclosed.
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