Centre National De La Recherche Scientifique

Universitéde Strasbourg

Polyplus Transfection

Aventis Pharma S.a.

Rhone-Poulenc Rorer S.a.

Pollyplus Transfection

Centre National De La Recherche Scientifique-Cnrs

Jean-Serge Remy

Jean-Paul Behr

Mitsuharu Kotera

Daniel Scherman

Barbara Demeneix

Bertrand Schwartz

Emilie Voirin

France Jean-Paul Behr

Nadege Pfender

Benedicte Pons

Bénédicte Pons

Nadège Pfender

The invention relates to cationic siRNAs, characterized in that they are double-stranded RNA fragments, grafted to the ends of which are oligocations, the number of cationic charges grafted being comparable to or greater than that of the anionic charges carried by the internucleoside phosphates of the RNA strands.

Cationic siRNAs, synthesis and use for RNA interference

The invention relates to oligonucleotide-oligocation molecules ABH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein .Ais an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2'-fluoro, 2&#x2032;-O-alkyl, or a marker group such as a fluorescent agent, .Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising .&#x2014;HPO&#x2014;R&#x2014;(X&#x2014;R)&#x2014;X&#x2014;R&#x2014;O&#x2014;, where R, Rn and R, identical or different, are lower alkylene, X is NH or NC(NH), n varies from 1 to 5 and n1=2 to 20, .&#x2014;HPO&#x2014;R&#x2014;CH(RX)&#x2014;R&#x2014;O&#x2014;, where Ris lower alkylene, Rand R, identical or different, are lower alkylene and Xis putrescine, spermidine or spermine residue, .&#x2014;HPO&#x2014;R-(aa)-R&#x2014;O&#x2014;, where Ris lower alkylene and Ris lower alkylene, serine, a natural aminoalcohol, (aa)is a peptide containing natural aminoacids with cationic side chains, such as Arginine, Lysine, Ornithine, -Histidine, Diaminopropionic acid and n2=2 to 20.

Cationic oligonucleotides, automated methods for preparing same and their uses

The invention relates to oligonucleotide-oligocation molecules ABH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein &#x2022;Ais an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2'-fluoro, 2&#x2032;-O-alkyl, or a marker group such as a fluorescent agent, &#x2022;Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising &#x2022;&#x2014;HPO&#x2014;R&#x2014;(X&#x2014;R)&#x2014;X&#x2014;R&#x2014;O&#x2014;, where R, Rn and R, identical or different, are lower alkylene, X is NH or NC(NH), n varies from 1 to 5 and n1=2 to 20, &#x2022;&#x2014;HPO&#x2014;R&#x2014;CH(RX)&#x2014;R&#x2014;O&#x2014;, where Ris lower alkylene, Rand R, identical or different, are lower alkylene and Xis putrescine, spermidine or spermine residue, &#x2022;&#x2014;HPO&#x2014;R-(aa)-R&#x2014;O&#x2014;, where Ris lower alkylene and Ris lower alkylene, serine, a natural aminoalcohol, (aa)is a peptide containing natural aminoacids with cationic side chains, such as Arginine, Lysine, Ornithine, -Histidine, Diaminopropionic acid and n2=2 to 20.

The present invention relates to compositions comprising at least one nucleic acid and one lipopolyamine, and their utilisation in gene therapy, particularly for the transfert in vivo of nucleic acids.

Composition containing nucleic acids, preparation and uses

Growing community of inventors

Neugartheim, France

Jean-Serge Remy