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Nucleic acid-containing composition, its preparation and use
| Details |
Inventors: Bazile, Didier; Emile, Carole; Helene, Claude; Spenlehauer, Gilles;
Assignee: Rhone-Poulenc Rorer SA (Anthony Cedex, FR)
Primary Examiner: Guzo; David
Assistant Examiner: Wang; Andrew
Attorney, Agent or Firm: Hansen; Christine M.
The present invention relates to compositions comprising nucleic acids and oligopeptides, and their use in therapy and in gene therapy, in particular for the transfer of nucleic acids. |
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DETAILED DESCRIPTION We claim: 1.
A composition comprising a deoxyribonucleic acid and a cationic oligopeptide that forms secondary structures, wherein the oligopeptide corresponds to the formula (A.
sub.
0 A.
sub.
y A.
sub.
y A.
sub.
0)n (SEQ ID NO:1) or (A.
sub.
0 A.
sub.
y A.
sub.
0 A.
sub.
y)n (SEQ ID NO:2) in which A.
sub.
0 is a hydrophobic amino acid, A.
sub.
y is a hydrophilic amino acid and n is an integer greater than or equal to 4.
2.
The composition according to claim 1, characterized in that the oligopeptide forms .
alpha.
helices or .
beta.
sheets.
3.
The composition according to claim 1, characterized in that the hydrophobic amino acid is chosen from leucine, valine, isoleucine and phenylalanine.
4.
The composition according to claim 1, characterized in that the hydrophilic amino acid is chosen from lysine, arginine and histidine.
5.
The composition according to claim 1, characterized in that the oligopeptide is chosen from (LKKL)n (SEQ ID NO:3), (LKLK)n (SEQ ID NO:4) and (LRRL)n (SEQ ID NO:5).
6.
The composition according to claim 5, characterized in that n is between 4 and 100.
7.
The composition according to claim 1, characterized in that the deoxyribonucleic acid is chemically modified.
8.
The composition according to claim 1, characterized in that the deoxyribonucleic acid is an antisense sequence.
9.
The composition according to claim 1, characterized in that the deoxyribonucleic acid contains a therapeutic gene.
10.
The composition according to claim 1, characterized in that the ratio of positive charges of the oligopeptide to negative charges of the deoxyribonucleic acid is greater than or equal to 1.
11.
A vector for the transfer of deoxyribonucleic acids comprising a composition according to claim 1.
12.
The vector of claim 11, characterized in that it is a nanoparticle, a liposome or a low density lipoprotein.
13.
A method of encapsulation of deoxyribonucleic acids in transfer vectors, comprising: (a) combining the transfer vector or its components and a composition according to claim 1 under conditions permitting encapsulation of the deoxyribonucleic acid in the transfer vector, and (b) recovering the transfer vector that is formed
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Gene Therapy 
