摘要:
Chimeric oligonucleotide of the formula 5'-W-X1-Y-X2-Z-3', where W represents a 5'-O-alkyl nucleotide, each of X?1 and X2¿ 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(CH¿2?CH2NH2)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.
摘要:
Different-sequence peptoids, including lipid-and sterol-conjugated peptoids, are found to be effective in transfection of cells with oligonucleotides. Combinatorial libraries of such peptoids can be screened efficiently in a high-throughput format, and selected peptoids are identified post-screening.
摘要:
Inhibitors of laminin5beta3 are provided that reduce the expression or biological activities of laminin5beta3 or the expression of laminin5beta3 mRNA in a mammalian cell. Laminin5beta3 inhibitors include antisense molecules, ribozymes, antibodies and antibody fragments, proteins and polypeptides as well as small molecules. Laminin5beta3 inhibitors find use in compositions and methods for decreasing laminin5beta3 gene expression as well as methods for inhibiting the proliferation of mammalian cells, including tumor cells of epithelial origin, and methods for treating neoplastic diseases.
摘要:
Inhibitors of TSPAN-7 are provided that reduce the expression or biological activities of TSPAN-7 in a mammalian cell. TSPAN-7 inhibitors include antisense molecules, ribozymes, antibodies and antibody fragments, proteins and polypeptides as well as small molecules. TSPAN-7 inhibitors find use in compositions and methods for decreasing TSPAN-7 gene expression as well as methods for inhibiting proliferation of mammalian cells, including tumor cells, methods for decreasing the side effects of cancer therapy and methods for treating neoplastic diseases. Also provided are nucleic acids encoding a new member of the tetraspan family, TSPAN-7, and polypeptides encoded thereby.