IP Library Granted Patent US 10,344,300
Granted Patent B2
US 10,344,300 · App. 14/662,334 · Granted Jul 9, 2019

Nanotubes as carriers of nucleic acids into cells

Inventors: Yunpeng Chen (Mansfield, MA); Qian Chen (Barrington, RI); Thomas J. Webster (Barrington, RI); Hicham Fenniri (Edmonton, CA); Usha Devi Hemraz (Edmonton, CA)
Assignees: Brown University; Rhode Island Hospital; The Governors of the University of Alberta; National Research Council of Canada
C12N15/87A61K9/0092A61K31/675A61K31/713A61K48/005A61K48/0075C12N15/113C12N15/115C12Q1/6841B82Y5/00C12N2310/12C12N2310/14C12N2310/141C12N2320/30
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Quick Facts
Patent No.
US 10,344,300
App. No.
14/662,334
Granted
Jul 9, 2019
Kind
B2
Abstract

The present invention is directed to transfection complexes of rosette nanotubes and one or more nucleic acids.

Claims (25)

1. A method of delivering one or more nucleic acids into a cell comprising contacting the cell with a complex of the one or more nucleic acids and a structure formed from the assembly of one or more compounds in aqueous media having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof in a manner to deliver the complex into the cell.

2. A complex comprising one or more nucleic acids and a structure formed from the assembly of compounds having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof.

3. The method of claim 1 wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated.

4. The complex of claim 2 wherein the aliphatic moiety is a straight chain or a branched alkyl group being saturated or unsaturated.

5. The method of claim 1 wherein R 2 is the linker group (CH 2 ) n where n is 1, 2, 3 or 4 and Y is lysine.

6. A method of delivering one or more nucleic acids into a cell comprising contacting the cell with a complex of the one or more nucleic acids and a structure formed from the assembly of one or more compounds in aqueous media having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an a-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof in a manner to deliver the complex into the cell, wherein the one or more nucleic acids include DNA, RNA, a gene, a gene fragment, an exon, an intron, intergenic DNA, heterochromatic DNA, messenger RNA, transfer RNA, interference RNA, dsRNA, ssRNA, saRNA, siRNA, miRNA, ribosomal RNA, a ribozyme, cDNA, a recombinant polynucleotide, a branched polynucleotide, a plasmid, a vector, isolated DNA of a sequence, isolated RNA of a sequence, a nucleic acid probe, a molecular beacon or a primer.

7. A method of delivering one or more nucleic acids into a cell comprising contacting the cell with a complex of the one or more nucleic acids and a structure formed from the assembly of one or more compounds in aqueous media having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof in a manner to deliver the complex into the cell, wherein the one or more nucleic acids includes siRNA having between about 10 to about 30 nucleic acids in length.

8. A method of delivering one or more nucleic acids into a cell comprising contacting the cell with a complex of the one or more nucleic acids and a structure formed from the assembly of one or more compounds in aqueous media having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof in a manner to deliver the complex into the cell, wherein the cell includes an animal, plant or bacterial cell.

9. The method of claim 1 wherein the linker group is (CH 2 ) n where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO,

10. The complex of claim 2 wherein the linker group is (CH 2 ) n where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO,

11. A method of making a complex comprising mixing together one or more compounds having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof

and one or more nucleic acids in aqueous media to form a stable complex of the one or more compounds and the one or more nucleic acids in aqueous media.

12. A method of making a complex comprising mixing together one or more compounds having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof

and one or more nucleic acids in aqueous media to form a stable complex of the one or more compounds and the one or more nucleic acids in aqueous media, wherein the linker group is (CH 2 ) n , where n is an integer of 1, 2, 3, or 4, (CH 2 ) 3 CO,

13. A method of making a complex comprising mixing together one or more compounds having the formula

wherein X is CH or nitrogen; R 2 is hydrogen or a linker group; Y is absent when R 2 is hydrogen or is an amino acid or polypeptide having an amino group covalently bound to an α-carbon of the amino acid and the amino group is covalently bound to the linker group R 2 ; and R 1 is hydrogen or an aliphatic moiety; and salts thereof

and one or more nucleic acids in aqueous media to form a stable complex of the one or more compounds and the one or more nucleic acids in aqueous media, wherein the mixture is sonicated to form the stable complex in aqueous media.

14. The method of claim 11 wherein the mixture is sonicated and heated to boiling to form the stable complex in aqueous media.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 6, 2017
From: HEMRAZ, USHA DEVI
To: THE GOVERNORS OF THE UNIVERSITY OF ALBERTA
Reel/Frame 044318/0364 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 6, 2017
From: FENNIRI, HICHAM
To: NATIONAL RESEARCH COUNCIL OF CANADA
Reel/Frame 044318/0470 →
CONFIRMATORY LICENSE Recorded Apr 7, 2015
From: BROWN UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 035378/0827 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 19, 2015
From: CHEN, YUPENG; CHEN, QIAN; WEBSTER, THOMAS J.
To: BROWN UNIVERSITY; RHODE ISLAND HOSPITAL
Reel/Frame 035202/0246 →
Continuity (3)
Continuation 13977138
Provisional Application 61429555 · Jan 4, 2011
Related Publication 20150258213A1 · Sep 17, 2015
Cited By (1)
US 12,534,468