Methods for delivering compounds into a cell

• US 6,638,767 B2
• Filed: 12/21/2000
• Issued: 10/28/2003
• Est. Priority Date: 05/01/1996
• Status: Expired due to Fees

• Current Assignee: Cerevast Therapeutics, Inc.
• Original Assignee: Imarx Pharmaceutical Corp. (Sycamore Entertainment Group, Inc.)
• Inventors: McCreery, Thomas, Unger, Evan C.
• Primary Examiner(s): Ketter, James
• Assistant Examiner(s): Sullivan, Daniel M.
• Application Number:
  US09/742,938
• Publication Number:
  US 20010031740A1
• Time in Patent Office: 1,041 Days
• Field of Search: 514/44, 435/458, 435/455
• US Class Current: 435/458
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 15/88 using microencapsulation, e.g. using amphiphile liposome vesicle

Abstract

The present invention is directed, inter alia, to a method for delivering a compound into a cell comprising administering to the cell the compound to be delivered, an organic halide, and/or a carrier. Ultrasound may also be applied, if desired.

Claims

1. A method of expression an exogenous nucleic acid sequence in a cell, the method comprising the steps of:

delivering said exogenous nucleic acid sequence together with a halide compound into said cell; and

applying ultrasound to said cell sufficient to express said exogenous nucleic acid sequence in said cell,

wherein said delivering and said applying steps are conducted concurrently.

2. A method of expressing an exogenous nucleic acid sequence in a cell, said method comprising the steps of:

delivering said exogenous nucleic acid sequence together with a halide compound into said cell; and

applying ultrasound to said cell sufficient to facilitate expression of said exogenous nucleic acid sequence in said cell,

wherein said halide compound is selected from the group consisting of 1-bromo-nonafluorobutane;

perfluorooctyliodide;

perfluorooctylbromide;

1-chloro-1-fluoro-1-bromomethane;

1,1,1-trichloro-2,2,2-trifluoroethane;

1,2-dichloro-2,2-difluoroethane;

1,1-dichloro-1,2-difluoroethane;

1,2-dichloro-1,1,3-trifluoropropane;

1-bromoperfluorobutane;

1-bromo-2,4-difluorobenzene;

2-iodo-1,1,1-trifluoroethane;

5-bromovaleryl chloride;

1,3-dichlorotetrafluoroacetone;

bromine pentafluoride;

1-bromo-1,1,2,3,3,3-hexafluoropropane;

2-chloro 1,1,1,4,4,4-hexafluoro-2-butene;

2-chloropentafluoro-1,3-butadiene;

iodotrifluoroethylene;

1,1,2-trifluoro-2-chloroethane;

1,2-difluorochloroethane;

1,1-difluoro-2-chloroethane;

1,1-dichlorofluoroethane;

heptafluoro-2-iodopropane;

bromotrifluoroethane;

chlorotrifluoromethane;

dichlorodifluoromethane;

dibromofluoromethane;

chloropentafluorethane;

bromochlorodifluoromethane;

dichloro-1,1,2,2-tetrafluoroethane;

1,1,1,3,3-pentafluoropentane;

perfluorotributylamine;

perfluorotripropylamine;

3-fluorobenzaldehyde;

2-fluoro-5-nitrotoluene;

3-fluorostyrene;

3,5-difluoroaniline;

2,2,2-trifluoroethylacrylate;

3-(trifluoromethoxy)-acetophenone;

1,1,2,2,3,3,4,4-octafluorobutane;

1,1,1,3,3-pentafluorobutane;

1-fluorobutane;

1,1,2,2,3,3,4,4-octafluorobutane;

1,1,1,3,3-pentafluorobutane;

perfluoro-4 methylquinolizidine;

perfluoro-N-methyl-decahydroquinone;

perfluoro-N-methyl-decahydroisoquinone;

perfluoro-N-cyclohexyl-pyrrolidine;

tetradecaperfluoroheptane;

dodecaperfluorocyclohexane;

perfluoromethane;

perfluoroethane;

perfluoropane;

perfluorobutane;

perfluoropentane;

perfluorohexane;

perfluoroheptane;

perfluorooctane;

perfluorononane;

perfluorodecane;

perfluorododecane;

perfluoro-2-methyl-2-pentene;

perfluorocyclohexane;

perflurodecalin;

perfluorododecalin;

perfluoropropylene;

perfluorocyclobutane;

perfluoro-2-butyne;

perfluoro-2-butene;

perfluorobuta-1,3-diene;

perfluorobutylethyl ether;

bis(perfluoroisopropyl) ether;

bis(perfluoropropy) ether;

perfluorotetrahydropyran;

perfluoromethyl tetrahydrofuran;

perfluoro t-butyl methyl ether;

perfluoro isobutyl methyl ether;

perfluoro n-butyl methyl ether;

perfluoro isopropyl ethyl ether;

perfluoro n-propyl ethyl ether;

perfluoro cyclobutyl methyl ether;

perfluoro cyclopropyl ethyl ether;

perfluoro isopropyl methyl ether;

perfluoro n-propyl methyl ether;

perfluoro diethyl ether;

perfluoro cyclopropyl methyl ether;

perfluoro methyl ethyl ether;

perfluoro dimethyl ether;

sulfur hexafluoride; and

selenium hexafluoride;

wherein said delivering and said applying steps are conducted concurrently.

3. A method of expressing an exogenous nucleic acid sequence in a cell, the method comprising the steps of:

delivering said exogenous nucleic acid sequence together with a halide compound into said cell; and

applying ultrasound to said cell sufficient to express said exogeneous nucleic acid sequence in said cell,

wherein said delivering step is preceded by said applying step.

4. A method of expressing an exogenous nucleic acid sequence in a cell, said method comprising the steps of:

delivering said exogenous nucleic acid sequence together with a halide compound into said cell; and

applying ultrasound to said cell sufficient to facilitate expression of said exogenous nucleic acid sequence in said cell,

wherein said halide compound is selected from the group consisting of 1-bromo-nonafluorobutane;

perfluorooctyliodide;

perfluorooctylbromide;

1-chloro-1-fluoro-1-bromomethane;

1,1,1-trichloro-2,2,2-trifluoroethane;

1,2-dichloro-2,2-difluoroethane;

1,1-dichloro-1,2-difluoroethane;

1,2-dichloro-1,1,3-trifluoropropane;

1-bromoperfluorobutane;

1-bromo-2,4-difluorobenzene;

2-iodo-1,1,1-trifluoroethane;

5-bromovaleryl chloride;

1,3-dichlorotetrafluoroacetone;

bromine pentafluoride;

1-bromo-1,1,2,3,3,3-hexafluoropropane;

2-chloro 1,1,1,4,4,4-hexafluoro-2-butene;

2-chloropentafluoro-1,3-butadiene;

iodotrifluoroethylene;

1,1,2-trifluoro-2-chloroethane;

1,2-difluorochloroethane;

1,1-difluoro-2-chloroethane;

1,1-dichlorofluoroethane;

heptafluoro-2-iodopropane;

bromotrifluoromethane;

chlorotrifluoromethane;

dichlorodifluoromethane;

dibromofluoromethane;

chloropentafluoroethane;

bromochlorodifluoromethane;

dichloro-1,1,2,2-tetrafluoroethane;

1,1,1,3,3-pentafluoropentane;

perfluorotributylamine;

perfluorotripropylamine;

3-fluorobenzaldehyde;

2-fluoro-5-nitrotoluene;

3-fluorostyrene;

3,5-difluoroaniline;

2,2,2-trifluoroethylacrylate;

3-(trifluoromethoxy)-acetophenone;

1,1,2,2,3,3,4,4-octafluorobutane;

1,1,1,3,3-pentafluorobutane;

1-fluorobutane;

1,1,2,2,3,3,4,4-octafluorobutane;

1,1,1,3,3-pentafluorobutane;

perfluoro-4 methylquinolizidine;

perfluoro-N-methyl-decahydroquinone;

perfluoro-N-methyl-decahydroisoquinone;

perfluoro-N-cyclohexyl-pyrrolidine;

tetradecaperfluoroheptane;

dodecaperfluorocyclohexane;

perfluoromethane;

perfluorethane;

perfluoropropane;

perfluorobutane;

perfluoropentane;

perfluorohexane;

perfluoroheptane;

perfluorooctane;

perfluorononane;

perfluorodecane;

perfluorodecane;

perfluoro-2-methyl-2-pentene;

perfluorocyclohexane;

perfluorodecalin;

perfluorododecalin;

perfluoropropylene;

perfluorocyclobutane;

perfluoro-2-butyne;

perfluoro-2-butene;

perfluorobuta-1,3-diene;

perfluorobutyethyl ether;

bis(perfluoroisopropyl) ether;

bis(perfluoropropyl) ether;

perfluorotetrahydropyran;

perfluoromethyl tetrahydrofuran;

perfluoro t-butyl methyl ether;

perfluoro isobutyl methyl ether;

perfluoro n-butyl methyl ether;

perfluoro isopropyl ethyl ether;

perfluoro n-propyl ethyl ether;

perfluoro cyclobutyl methyl ether;

perfluoro cyclopropyl ethyl ether;

perfluoro isopropyl methyl ether;

perfluoro n-propyl methyl ether;

perfluoro diethyl ether;

perfluoro cyclopropyl methyl ether;

perfluoro methyl ethyl ether;

perfluoro dimethyl ether;

sulfur hexafluoride; and

selenium hexafluoride;

wherein said delivering step is preceded by said applying step.