Lipocationic polymers and uses thereof
AssigneeBoard of Regents, The University of Texas System
InventorsDaniel J. Siegwart, Jing Hao, Kejin Zhou, Jason Miller, Petra Kos, Lian Xue
Life of this patent
Estimating the term…
Abstract
Polymers produced by ring opening polymerization which comprises an amino group that can be used in compositions to deliver a nucleic acid such as a miRNA or a siRNA. In some embodiments, compositions which comprise the polymers described herein and a nucleic acid are also provided herein. In some embodiments, these compositions are used to silence one or more genes in vivo or treat a disease or disorder.
Claims20
A method of silencing gene expression comprising contacting a composition comprising a nucleic acid and a polymer of the formula:
- wherein:
- X1 is alkyl(C≦18) or substituted alkyl(C≦18);
- X2 is hydrogen, alkyl(C≦18), or substituted alkyl(C≦18);
- R1 is -A-Z;
- wherein:
- A is an alkanediyl(C≦18) or substituted alkanediyl(C≦18);
- Z is —NR3R4;
- wherein:
- R3 and R4 are each independently selected from hydrogen, alkyl(C≦18), substituted alkyl(C≦18);
- or R3 and R4 are taken together and are alkanediyl(C≦18) or substituted alkanediyl(C≦18);
- R2 is alkyl(C≦24), alkenyl(C≦24), substituted alkyl(C≦24), or substituted alkenyl(C≦24);
- x and y are each independently 0, 1, 2, 3, 4, or 5;
- m and n are each independently an integer between 0 and 250, provided that at least one of m and n is greater than 1;
- and
- the repeating units defined by m and n are randomly distributed throughout the polymer;
- or a pharmaceutically acceptable salt thereof;
- with a cell comprising said gene.
A method of treating or preventing a disease or disorder comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising a polymer of the formula:
- wherein:
- X1 is alkyl(C≦18) or substituted alkyl(C≦18);
- X2 is hydrogen, alkyl(C≦18), or substituted alkyl(C≦18);
- R1 is -A-Z;
- wherein:
- A is an alkanediyl(C≦18) or substituted alkanediyl(C≦18);
- Z is —NR3R4;
- wherein:
- R3 and R4 are each independently selected from hydrogen, alkyl(C≦18), substituted alkyl(C≦18);
- or R3 and R4 are taken together and are alkanediyl(C≦18) or substituted alkanediyl(C≦18);
- R2 is alkyl(C≦24), alkenyl(C≦24), substituted alkyl(C≦24), or substituted alkenyl(C≦24);
- x and y are each independently 0, 1, 2, 3, 4, or 5;
- m and n are each independently an integer between 0 and 250, provided that at least one of m and n is greater than 1;
- and
- the repeating units defined by m and n are randomly distributed throughout the polymer;
- or a pharmaceutically acceptable salt thereof;
- and
- a therapeutic nucleic acid for the disease or disorder.
A method of preparing a polymer of the formula:
- wherein:
- X1 and X2 are independently selected from hydrogen, alkyl(C≦12), or substituted alkyl(C≦12);
- R1 is -A-Z;
- wherein:
- A is an alkanediyl(C≦12) or substituted alkanediyl(C≦12);
- Z is —NR3R4;
- wherein:
- R3 and R4 are each independently selected from hydrogen, alkyl(C≦12), substituted alkyl(C≦12);
- or R3 and R4 are taken together and are alkanediyl(C≦12) or substituted alkanediyl(C≦12);
- R2 is alkyl(C≦24), alkenyl(C≦24), substituted alkyl(C≦24), or substituted alkenyl(C≦24);
- x and y are each independently 0, 1, 2, 3, 4, or 5;
- and
- m and n are each independently an integer between 0 and 250, provided that at least one of m and n is greater than 1;
- and
- the repeating units defined by m and n are randomly distributed throughout the polymer;
- comprising reacting a first monomer of the formula:
- wherein:
- R1 is -A-Z;
- wherein:
- A is an alkanediyl(C≦12) or substituted alkanediyl(C≦12);
- Z is —NR3R4;
- wherein:
- R3 and R4 are each independently selected from hydrogen, alkyl(C≦12), substituted alkyl(C≦12);
- or R3 and R4 are taken together and are alkanediyl(C≦12) or substituted alkanediyl(C≦12);
- x is 0, 1, 2, 3, 4, or 5;
- with a second monomer of the formula:
- wherein:
- R2 is alkyl(C≦24), alkenyl(C≦24), substituted alkyl(C≦24), or substituted alkenyl(C≦24);
- and
- y is 0, 1, 2, 3, 4, or 5;
- in the presence of a base.
Dependencies are inferred from the claim text.