Endosomolytic agents and cell delivery systems
First Claim
1. An endosomal lysing polymer comprisingat least one hydrolyzable functional moiety selected from the group consisting of ortho-esters, hydrazones, and cis-acetonyls, wherein an endosomal lysing agent is released upon hydrolysis of the hydrolyzable functional moiety;
- and at least one ionizable functional moiety, wherein the ionizable functional moiety comprises a proton acceptor site and is operably linked to the hydrolyzable functional moiety;
wherein said polymer is capable of effecting the lysis of an endosome in response to a change in pH.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention provides improved cell delivery compositions. In particular, the invention provides biocompatible endosomolytic agents. In a preferred embodiment, the endosomolytic agents are also biodegradable and can be broken down within cells into components that the cells can either reuse of dispose of. In one aspect, the present invention provides endosomolytic agents capable of effecting the lysis of an endosome in response to a change in pH, and methods for effecting the lysis of an endosome. These inventive endosomolytic agents obviate the need for known agents (i.e., chloroquine, fusogenic peptides, inactivated adenoviruses and polyethyleneimine) that can burst endosomes and have negative effects on cells. In another aspect, the present invention provides cell delivery compositions comprising an endosomolytic component that is capable of effecting the lysis of the endosome in response to a change in pH, and an encapsulating, or packaging, component capable of packaging a therapeutic agent to be delivered to cellular or subcellular components.
36 Citations
34 Claims
-
1. An endosomal lysing polymer comprising
at least one hydrolyzable functional moiety selected from the group consisting of ortho-esters, hydrazones, and cis-acetonyls, wherein an endosomal lysing agent is released upon hydrolysis of the hydrolyzable functional moiety; - and
at least one ionizable functional moiety, wherein the ionizable functional moiety comprises a proton acceptor site and is operably linked to the hydrolyzable functional moiety;
wherein said polymer is capable of effecting the lysis of an endosome in response to a change in pH. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
- and
-
18. A biocompatible composition comprising:
-
a packaging agent, characterized by an ability to bind to a therapeutic agent and mediate import into endosomes; and
an endosomal lysing polymer comprising at least one hydrolyzable functional moiety selected from the group consisting of ortho-esters, hydrazones, and cis-acetonyls, wherein an endosomal lysing agent is released upon hydrolysis of the hydrolyzable functional moiety; and
at least one ionizable functional moiety, wherein the ionizable functional moiety comprises a proton acceptor site and is operably linked to the hydrolyzable functional moiety;
wherein said polymer is capable of effecting the lysis of an endosome in response to a change in pH. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
-
-
31. A method of lysing an endosome, the method comprising the steps of:
-
providing a composition for endosomal uptake into the cell; and
contacting the composition with the cell in the presence of an endosomal lysing polymer comprising at least one hydrolyzable functional moiety selected from the group consisting of ortho-esters, hydrazones, and cis-acetonyls, wherein an endosomal lysing agent is released upon hydrolysis of the hydrolyzable functional moiety; and
at least one ionizable moiety, wherein the ionizable functional moiety comprises a proton acceptor site and is operably linked to the hydrolyzable functional moiety;
wherein said polymer is capable of effecting the lysis of an endosome in response to a change in pH. - View Dependent Claims (34)
-
-
32. A method for introducing a nucleic acid into a cell or a subcellular component, the method comprising the steps of:
-
providing a biocompatible delivery composition comprising;
a packaging agent;
an endosomal lysing polymer comprising at least one hydrolyzable functional moiety selected from the group consisting of ortho-esters, hydrazones, and cis-acetonyls, wherein an endosomal lysing agent is released upon hydrolysis of the hydrolyzable functional moiety; and
at least one ionizable functional moiety, wherein the ionizable functional moiety comprises a proton acceptor site and is operably linked to the hydrolyzable functional moiety;
wherein said polymer is capable of effecting the lysis of an endosome in response to a change in pH; and
a nucleic acid; and
contacting the composition with cells. - View Dependent Claims (33)
-
Specification