CHIMERIC ANTISENSE OLIGONUCLEOTIDES AND CELL TRANSFECTING FORMULATIONS THEREOF

• Main Authors: INNIS, MICHAEL, A, REINHARD, CHRISTOPH, J, ZUCKERMANN, RONALD, N
• Format: Patent
• Language: English; French; German
• Published: 05.03.2008
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; DERIVATIVES THEREOF; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; SUGARS; VINEGAR; WINE

Chimeric oligonucleotide of the formula 5'-W-X -Y-X -Z-3', where W represents a 5'-O-alkyl nucleotide, each of X and X represented a block of seven to twelve phosphodiester-linked 2'-O-alkyl ribonucleotides, Y represents a block of five to twelve phosphorothioate-linked deoxyribonucleotides, and Z represents a blocking group effective to block nuclease activity at the 3' end of the oligonucleotide, are described. These compounds exhibit high resistance to endo- and exonucleases, high sequence specificity, and the ability to activate RNAse H, as evidenced by efficient and long-lasting suppression of target mRNA. The oligonucleotides are preferably transfected into cells in formulations containing a lipid-peptoid conjugate carrier molecule of the formula L-linker-[N(CH2CH2NH2)CH2(C=O)-N(CH2CH2R)CH2(C=O)-N(CH2CH2R)CH2(C=O)]3-NH2, where L is a lipid moiety, including a steroid, and each group R is independently selected from alkyl, aminoalkyl, and aralkyl.