PHOTOSENSITIZED TRYPANOSOMATIDS AND VACCINE COMPOSITIONS THEREOF

摘要

Disclosed herein are methods and compositions for the delivery of polypeptides, including vaccine candidate polypeptides, into mammalian cells comprising the use of photosensitized trypanosomatid organisms. Also disclosed are methods of treatment of trypanosomatid infections comprising administering phthalocyanine compounds or phthalocyanine-treated trypanosomatid microorganisms as vaccines, as well as and polypeptide delivery vectors comprising phthalocyanine-treated trypanosomatid microorganisms.

主权项

1. A composition for delivering a polypeptide into a mammalian cell, the composition comprising a trypanosomatid that has been treated with a compound of formula (I): or an acceptable salt thereof,
wherein L1 and L2 are independently selected from —O(C1-C6 alkyl), —O(C1-C6 alkenyl), —O(C1-C6 alkynyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, and —OR,wherein
each R is independently —[C1-C6 alkylene-O]m—R′ or —[C1-C6 alkylene-NR″]n—R′,each m and n are independently an integer selected from 1 to 20,each R′ is independently selected from H and C1-C6 alkyl,each R″ is independently selected from H and C1-C6 alkyl;each q is independently an integer selected from 0, 1, and 2; andR1, R2, R3, and R4 are independently selected from halogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkoxy, C1-C6 aryloxy, C1-C6 heteroaryloxy, and polyalkylene oxide, each optionally substituted with halogen, C1-C6 alkyl, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2; wherein the trypanosomatid expresses the polypeptide; and wherein the trypanosomatid is capable of entering the mammalian cell.