Polyamides for nucleic acid delivery
OwnerTheresa M. Reinekeinventor
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Abstract
A new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications, including, a gene transfer vector that has comparable efficiency to a viral vector without the potential for a life-threatening immune response is provided. Complexes including a cellular delivery molecule or agent that can facilitate the translocation of the complex or portion thereof into cells is also provided. The cellular delivery molecules may include one or more polymers, e.g., polyamides, dendritic macromolecules and carbohydrate-containing degradable polyesters.
Claims21
A method of delivering a biologically active molecule to a cell, the method comprising contacting the cell with a polyplex formed from an interaction between a biologically active molecule and a cellular delivery polymer, wherein:
- the cellular delivery polymer is a cyclodextrin-based dendritic macromolecule comprising a cyclodextrin core and an oligoamine shell attached to the cyclodextrin core, the cyclodextrin core comprising an alpha, beta, or gamma cyclodextrin and the oligoamine shell comprising polyamine chains depicted by one of the following formulae:
- wherein n is 1, 2, 3, or 4;
- or
- wherein n is 1, 2, 3, or 4;
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula A is formed from a reaction between an alpha, beta, or gamma cyclodextrin substituted with a group depicted by the following formula:
- and at least one linear polyamine depicted by the following formula:
- NH2—R—NH2 Formula D
- wherein each R is independently selected from the group consisting of:
- —(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2—, and —(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2;
- and
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula B is formed by a reaction between an alpha, beta, or gamma cyclodextrin substituted with an azide group and at least one linear polyamine depicted by the following formula:
- wherein n is 1, 2, 3, or 4.
A kit comprising at least one biologically active molecule and at least one cellular delivery polymer, wherein:
- the cellular delivery polymer is a cyclodextrin-based dendritic macromolecule formed from a reaction between a substituted cyclodextrin and a polyamine, and
- wherein the cyclodextrin-based dendritic macromolecule comprises a cyclodextrin core comprising alpha, beta, or gamma cyclodextrin and an oligoamine shell comprising polyamine chains, the polyamine chains being attached to the cyclodextrin core, and the polyamine chains being depicted by one of the following formulae:
- wherein n is 1, 2, 3, or 4;
- or
- wherein n is 1, 2, 3, or 4;
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula A is formed from a reaction between an alpha, beta, or gamma cyclodextrin substituted with a group depicted by the following formula:
- and at least one linear polyamine depicted by the following formula:
- NH2—R—NH2 Formula D
- wherein each R is independently selected from the group consisting of:
- —(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH—(CH2)2—NH(CH2)2—, and —(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2;
- and
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula B is formed by a reaction between an alpha, beta, or gamma cyclodextrin substituted with an azide group and at least one linear polyamine depicted by the following formula:
- wherein n is 1, 2, 3, or 4.
A complex comprising a cellular delivery polymer and an agent that is desirably taken up by cells, wherein:
- the cellular delivery polymer is a cyclodextrin-based dendritic macromolecule comprising a cyclodextrin core comprising alpha, beta, or gamma cyclodextrin and an oligoamine shell comprising polyamine chains, the polyamine chains being attached to the cyclodextrin core, and the polyamine chains being depicted by one of the following formulae:
- wherein n is 1, 2, 3, or 4;
- or
- wherein n is 1, 2, 3, or 4;
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula A is formed from a reaction between an alpha, beta, or gamma cyclodextrin substituted with a group depicted by the following formula:
- and at least one linear polyamine depicted by the following formula:
- NH2—R—NH2 Formula D
- wherein each R is independently selected from the group consisting of:
- —(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH—(CH2)2—, —(CH2)2—NH—(CH2)2—NH(CH2)2—NH(CH2)2—, and —(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2—NH—(CH2)2;
- and
- wherein the cyclodextrin-based dendritic macromolecule comprising the polyamine chains depicted by Formula B is formed by a reaction between an alpha, beta, or gamma cyclodextrin substituted with an azide group and at least one linear polyamine depicted by the following formula:
- wherein n is 1, 2, 3, or 4;
- and
- wherein the agent is at least one nucleic acid molecule or at least one polypeptide or both.
A cyclodextrin-based dendritic macromolecule depicted by one of the following structural formulae:
- wherein n is 1, 2, 3, or 4;
- or
- wherein n is 1, 2, 3, or 4.
Dependencies are inferred from the claim text.