SYSTEMS AND METHODS OF DELIVERY OF BIOACTIVE AGENTS USING BACTERIAL TOXIN-DERIVED TRANSPORT SEQUENCES

摘要

The field of the present invention relates, in part, to a strategy for novel pharmaceutical applications. More specifically, the present invention relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A386 (Cholix386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. Importantly, the systems and methods described herein provide for the following: the ability to deliver macromolecule doses without injections; the ability to deliver cargo, such as (but not limited to) siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes, which otherwise would have been impeded due to the barrier properties of most such membranes.

主权项

1. An isolated delivery construct comprising:
(a) a non-toxic Cholix toxin, wherein the Cholix construct has a mutation in domain Ill that renders the construct non-toxic; and (b) a therapeutic cargo.