发明名称 |
Complex and method for enhancing nuclear delivery |
摘要 |
The use of at least one nucleic acid based nuclear localization signal including a natural or synthetic m3G-CAP is shown to increase transmembrane transport of a molecular cargo, in particular large molecules, into the nucleus. The use of natural and synthetic m3G-CAP is disclosed and the effect shown with a natural RNA 5′ end nuclear localization signal composed of a 2,2,7-trimethylguanosine CAP (m3G-CAP) coupled to fluorescent Streptavidin in one example, and an antisense oligonucleotide in another. A methylenephosphonate modified m3G-CAP is shown to have improved stability in human serum and in cytosolic extract. |
申请公布号 |
US9067964(B2) |
申请公布日期 |
2015.06.30 |
申请号 |
US200913140070 |
申请日期 |
2009.12.17 |
申请人 |
Oligomer Sciences AB |
发明人 |
Smith Edvard;Moreno Pedro;Strömberg Roger;Wenska Malgorzata |
分类号 |
A01N43/04;A61K31/70;C07H19/167;A61K31/7056;A61K31/7084;A61K31/7076;A61K31/7064;A61K31/708;A61K31/7042;A61K31/706;A61K31/7052;A61K31/7115;A61K31/712;C07H19/20;C07H19/207;C07H21/02 |
主分类号 |
A01N43/04 |
代理机构 |
Renner, Otto, Boisselle & Sklar, LLP |
代理人 |
Renner, Otto, Boisselle & Sklar, LLP |
主权项 |
1. A complex for facilitating transmembrane transport of a molecular cargo into the nucleus of a mammalian cell, wherein said complex comprises a molecular cargo coupled to a synthetic m3G-CAP or an analogue thereof, wherein said molecular cargo is linked by covalent or non-covalent attachment to at least one modified 2,2,7-trimethylguanosine CAP structure as specified in Formula (I) wherein R1 is a cargo attached directly or a mono-, di- or oligonucleotide (modified or unmodified) followed by a cargo unless the cargo is attached through R2 then R1 is a hydroxyl or a phosphate mono or diester; R2 is methyl or any unsubstituted or substituted alkyl group or is a cargo attached directly or a mono-, di- or oligonucleotide (modified or unmodified) followed by a cargo; R3 is O or CH2; R4 is O or CH2; R5 is O or CH2; R6 is O or CH2; X is OH or SH, or salts thereof; Y is OH or SH, or salts thereof; Z is OH or SH, or salts thereof; R7 is O, Or CH2; R8 is NH2, H, or OH; R9 is H, NH2 or OH; R10 is OH, or F; and R11 is OH, Or OCH3, and wherein “base” is a purine or a pyrimidine base selected from uracil, cytosine, adenine, quinine or thymine or derivatives thereof. |
地址 |
Djursholm SE |