Polymers for delivery of nucleic acids
AssigneeThe Johns Hopkins University School of Medicine
InventorsHai-Quan Mao, Kevin Y. Lin, Bart S. Hendriks, Kam W. Leong, Michael F. Haller
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Abstract
The present invention relates to compositions and methods for delivery of nucleic acids. In particular, the invention provides a polymeric delivery formulation including a nucleic acid to be transfected into a host cell, formulated in a biodegradable polymer having phosphorous-based linkages.
Claims29
A composition for delivery of a nucleic acid, comprising:
- a nucleic acid formulated in a biocompatible polymer having recurring monomeric elements in said polymer represented in general formula (XV):
- wherein, independently for each occurrence:
- Q1 represents O or S;
- Q2 represents O, S or NR′;
- X represents O, S or NR′;
- n is an integer of about five or more;
- R′ represents H or alkyl;
- R represents an organic or organometallic moiety;
- R1 represents hydrogen, alkyl, —O-alkyl, —O-cycloalkyl, aryl, —O-aryl, heterocycle, —O-heterocycle, —S—R4, —O—(C═O)—R4, —Cl or —N(R2)R3;
- R2 and R3, each independently, represent a hydrogen, an alkyl, an alkenyl, —(CH2)n-R4, or R2 and R3 taken together with the N atom to which they are attached complete a heterocycle having from 4 to about 8 atoms in the ring structure;
- and
- R4 represents a hydrogen, aryl, cycloalkyl, cycloalkenyl, heterocycle or polycycle.
A method for causing ectopic expression of a recombinant gene in myocytic cells of an animal, comprising:
- administering to an animal, by intramuscular administration, a polymeric composition comprising a recombinant gene formulated in a biocompatible polymer having recurring monomeric elements in said polymer represented in general formula (XV):
- wherein, independently for each occurrence:
- Q1 represents O or S;
- Q2 represents O, S or NR′;
- X represents O, S or NR′;
- n is an integer of about five or more;
- R′ represents H or alkyl;
- R represents an organic or organometallic moiety;
- R1 represents hydrogen, alkyl, —O-alkyl, —O-cycloalkyl, aryl, —O-aryl, heterocycle, —O-heterocycle, —S—R4, —O—(C═O)—R4, —Cl or —N(R2)R3;
- R2 and R3, each independently, represent a hydrogen, an alkyl, an alkenyl, —(CH2)n-R4, or R2 and R3 taken together with the N atom to which they are attached complete a heterocycle having from 4 to about 8 atoms in the ring structure;
- and
- R4 represents a hydrogen, aryl, cycloalkyl, cycloalkenyl, heterocycle or polycycle,
- wherein said polymeric composition is administered in an amount sufficient to result in transfection of myocytic cells of said animal by said recombinant gene, thereby causing ectopic expression of a recombinant gene in myocytic cells of an animal.
A method for preparing a biocompatible composition to transfect a cell in vivo, comprising combining a nucleic acid and a biocompatible polymer having recurring monomeric elements represented in general formula (XV):
- wherein, independently for each occurrence:
- Q1 represents O or S;
- Q2 represents O, S or NR′;
- X represents O, S or NR′;
- n is an integer greater than about 5;
- R′ represents H or alkyl;
- R represents an organic or organometallic moiety;
- R1 represents hydrogen, alkyl, —O-alkyl, —O-cycloalkyl, aryl, —O-aryl, heterocycle, —O-heterocycle, —S—R4, —O—(C═O)—R4, —Cl or —N(R2)R3;
- R2 and R3, each independently, represent a hydrogen, an alkyl, an alkenyl, —(CH2)n-R4, or R2 and R3 taken together with the N atom to which they are attached complete a heterocycle having from 4 to about 8 atoms in the ring structure;
- and
- R4 represents a hydrogen, aryl, cycloalkyl, cycloalkenyl, heterocycle or polycycle;
- wherein a biocompatible composition is prepared.
Dependencies are inferred from the claim text.