Abstract: Disclosed is a method for producing genetically engineered cells in vitro. The method includes direct injection of a genome editing composition into a cell nucleus of a cell. The genome editing composition includes at least one Cas protein and at least one gRNA molecule to target a distinct genomic location. The injection is performed with a microelectromechanical systems injection chip including a cantilever. The cantilever includes a microchannel being in fluid communication with a nanosyringe, and wherein direct injection includes providing a fluid communication between the microchannel and the nucleus of the cell by insertion of the nanosyringe into the nucleus of the cell and injecting the genome editing composition via the microchannel through the nanosyringe into the nucleus of the cell.

Abstract: 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.

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein .Ai is 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?-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 .—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, .

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein .Ai is 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?-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 .—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, .

Abstract: The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3?N1N2 . . . Ni-1Ni . . . Nj5? wherein—3?Ni . . . Nj5? is half of a double-stranded 19-28 mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3?N1 . . . Ni-15? is a 3-50 mer overhang of sequence allowing oligomerization of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein •Ai is 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?-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 •—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, •—HPO3—R4—CH(R5X1)—R6—O—, where R4 is lower alkylene, R5 and R6, identical or different, are lower alkylene

Abstract: The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3?N1N2 . . . Ni-1Ni . . . Nj5? wherein—3?Ni . . . Nj5? is half of a double-stranded 19-28 mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3?N1 . . . Ni-15? is a 3-50 mer overhang of sequence allowing oligomerisation of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.

Abstract: The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3?N1N2 . . . Ni-1Ni . . . Nj5? wherein—3?Ni . . . Nj5? is half of a double-stranded 19-28mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3?N1 . . . Ni-15? is a 3-50mer overhang of sequence allowing oligomerization of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.

Abstract: The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, —X is N—R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3-C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyl, A? is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.

Abstract: 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.

Abstract: The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, —X is N—R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3-C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyl, A- is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein. Ai is 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?-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 .—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, .

Abstract: The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3?N1N2 . . . Ni?1Ni . . . Nj5? wherein—3Ni . . . Nj5? is half of a double-stranded 19-28 mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3?N1 . . . Ni?15? is a 3-50 mer overhang of sequence allowing oligomerisation of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.

Abstract: A non-viral transfection vector which is to be delivered into the nucleus of a cell comprises a DNA molecule that is equipped with 1 to 25 NLS conjugates. Each conjugate comprises a nuclear localization signal (NLS) covalently linked to an oligonucleotide. The NLS conjugate may be covalently linked to one or both termini of a linear DNA molecule, associated with a plasmid DNA molecule by forming a triple helix, or inserted in a plasmid DNA molecule by strand invasion. The transfection vector is useful for gene therapy applications.

Abstract: 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.

Abstract: Compositions containing one or more nucleic acids and cationic polymers, and their use in gene therapy, particularly for in vivo nucleic acid transfer.