Branched poly(-amino esters) for the delivery of nucleic acids
AssigneesMassachusetts Institute of Technology, The Brigham and Women's Hospital Inc. B
InventorsCarlo Giovanni Traverso, Ameya R. Kirtane, Robert S. Langer, Hyunjoon Kim, Gary W. Liu, James Byrne, Daniel Reker, Yunhua Shi, Grace Junyue Zhong, Netra Rajesh Rajesh
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Abstract
The present disclosure provides branched poly(β-amino esters) (PBAEs) of Formula (I) made by reacting primary amines with diacrylates. Further provided herein are compositions comprising the polymers of Formula (I), and methods of using the compositions and polymers as described herein for the treatment of disease.
Claims22
1-123. (canceled)
A method of delivering an agent to a subject, tissue, or cell, the method comprising administering to the subject or contacting the tissue or cell with a composition comprising:
- a branched polymer of Formula (I):
- L-Rn (I)
- or a salt thereof, wherein:
- L is a substituted or unsubstituted heteroalkylene;
- n is 3, 4, 5, or 6;
- and
- each R is independently hydrogen, Formula (II), or Formula (III);
- wherein Formula (II) is:
- wherein:
- m is an integer of 1-1000, inclusive;
- A is optionally substituted alkylene or optionally substituted heteroalkylene;
- X is —CH═CH2, —CH2CH2OR2, —CH2CH2SR3, —CH2CH2N(R2)(R3), or —CH2CH2L(R4)q;
- q is 2, 3, 4, or 5;
- R1 is optionally substituted alkyl or optionally substituted heteroalkyl;
- R2 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;
- R3 is optionally substituted alkyl or optionally substituted heteroalkyl;
- or
- R2 and R3 combine to form a 4-7 membered ring;
- and
- each R4 is independently hydrogen, Formula (II), or Formula (III);
- wherein Formula (III) is:
- wherein:
- p is an integer of 1-1000, inclusive;
- B is optionally substituted alkylene or optionally substituted heteroalkylene;
- Z is —CH═CH2, —CH2CH2OR6, —CH2CH2SR7, —CH2CH2N(R6)(R7), or —CH2CH2L(R8)v;
- v is 2, 3, 4, or 5;
- R5 is optionally substituted alkyl or optionally substituted heteroalkyl;
- R6 is hydrogen, optionally substituted alkyl, or optionally substituted heteroalkyl;
- R7 is optionally substituted alkyl or optionally substituted heteroalkyl;
- or
- R6 and R7 combine to form a 4-7 membered ring;
- and
- each R8 is independently hydrogen, Formula (II), or Formula (III);
- provided that at least one R is Formula (II) or Formula (III), and provided that Formula (II) and Formula (III) are not the same;
- and
- an agent, wherein the agent is a polynucleotide.
127-130. (canceled)
The method of claim 1, wherein A is substituted or unsubstituted C1-10 alkylene or substituted or unsubstituted C1-10 heteroalkylene;
- and X is —CH2CH2N(R2)(R3) or —CH2CH2L(R4)q.
The method of claim 1, wherein B is substituted or unsubstituted C1-10 alkylene or substituted or unsubstituted C1-10 heteroalkylene;
- and Z is —CH2CH2N(R6)(R7) or —CH2CH2L(R8)v.
The method of claim 1, wherein n is 3, 4, or 6.
Dependencies are inferred from the claim text.