Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1997-04-16
1999-05-25
Degen, Nancy
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
4351721, 514 44, 554 1, 554103, 554124, 554227, C12P 2102, C07C 5300, C07C22900, C12N 1564
Patent
active
059069228
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to a method of introducing compounds, in particular nucleic acids, into cells. Further, the present invention relates to compositions for use in this method.
There are a number of situations in which it is desirable to deliver specific compounds into cells. One of these applications is the transfection of eucaryotic cells with DNA. This is currently done using various commercial agents such as "Transfectam" (Promega), "DOTAP", (Boehringer Mannheim), "Lipofectin" or "Lipofectamine" (BRL), or by using calcium phosphate mediated transfection.
The ability to deliver nucleic acid based compounds to cells also has application in drug delivery and gene therapy. The delivery of compounds into cells will change in association with a compound of the formula described below. Such changes may be manifested as modifications to their duration of action, ( e.g. slow release or sustained action) the amount of drug required or the mode of delivery. Delivery into cells using compounds variant within the parameters described below may also enable cell or tissue-specific targeting of drugs.
The present inventors have found that association of molecules with compounds modified with fatty acid acyl derivatives, of the general formula below, facilitates delivery of those compounds into cells.
SUMMARY OF THE INVENTION
Accordingly, in a first aspect the present invention consists of a method for introducing nucleic acid into a cell comprising exposing the cell to a compound having the formula: ##STR2## in which: w is a nucleic acid is absent
R.sub.4 is H or CH.sub.2 O--R.sub.3 ; and R.sub.1, R.sub.2 and R.sub.3 are the same or different and are either hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid having a carbon chain of 3 to 24 carbon atoms saturated or unsaturated, with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is an acyl group derived from a fatty acid.
In a second aspect the present invention consists of a method for introducing nucleic acid into a cell comprising exposing the cell to a compound having the formula: is absent 3 to 24 carbon atoms saturated or unsaturated.
In a third aspect the present invention consists in a compound for use in introducing nucleic acid into a cell, the compound having the formula ##STR3## in which: w is a nucleic acid is absent the same or different and are either hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid having a carbon chain of 3 to 24 carbon atoms saturated or unsaturated, with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is an acyl group derived from a fatty acid.
In a fourth aspect the present invention consists in a compound for use in introducing nucleic acid into a cell, the compound having the formula: is absent 3 to 24 carbon atoms saturated or unsaturated.
In a preferred form of each of the aspects of the present invention y is present.
In a preferred embodiment of the present invention the nucleic acid is DNA, RNA or oligonucleotides of either DNA or RNA, modified oligonucleotides or a combination of these. The nucleic acid may also bear chemical additives such as fluorescein (FITC), cholesterol, biotin or radiolabel.
The method of the present invention may be used for the delivery of nucleic acids including DNA, RNA, oligonucleotides of either DNA or RNA, modified oligonucleotides or a combination of these, to eucaryotic cells including established cell lines of animal or plant origin, primary cell lines of animal or plant origin, whole animals and plants whether applied systemically or topically or by aerosol. In this regard reference is made to EPO424688, the disclosure of which is incorporated herein by reference. The nucleic acid may also bear chemical additives such as fluorescein (FITC), cholesterol, biotin or radiolabel.
The method of the present invention is generally envisaged to involve the application of the compound in an essentially aqueous mixture to the surface of the cells of interest. However, in the ca
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Newkome et al. "Polytryptophane terminated dendritic macromolecules," Tetrahedron: Asymmetry, v.2, pp. 975-960.
Orkin et al "Report & Recommendations of the Panel to Assess The NIH Investment in Research on Gene Therapy", 1995.
Fiani et al "Selective Targeting of Drugs" TIBTECH vol. 7 57-61, 1989.
Bender Veronika
Cameron Fiona Helen
Jennings Philip Anthony
Moghaddam Minoo
Whittaker Robert George
Commonwealth Scientific and Industrial Research Organisation
Degen Nancy
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