PIRIE, Christopher, Michael,LIU, David, Victor,YANG, Nicole,WITTRUP, Karl, Dane
申请号：
USUS2012/020567
公开号：
WO2012/094653A3
申请日:
2012.01.07
申请国别(地区):
WO
年份:
2012
代理人:
摘要：
The present invention features compositions and methods for delivering a therapeutic agent to the cytoplasm of a cell. We have developed, inter alia, a system in which two or more distinct moieties - at least one therapeutic moiety and at least one potentiating moiety - selectively target and specifically bind cell surface molecules that are then internalized to an intracellular, membrane-bound compartment, such as an endosome. In some embodiments, as discussed further below, a third moiety that induces clustering of the targeted cell surface molecule can also be employed. Regardless of whether the compositions and methods include two or three moieties, the therapeutic agent can be any agent one wishes to deliver to the cytoplasm of a cell, and the potentiating agent can be any agent that destabilizes the intracellular, sub-cellular compartment in which the therapeutic agent is sequestered. The potentiating moiety can include, for example, a lytic agent (i.e., an agent that lyses or otherwise increases the permeability of the membrane of the intracellular compartment containing the therapeutic agent). To direct the various moieties of the system, including the therapeutic, potentiating, and clustering moieties, to a selected cellular target, any of the moieties can include a binding agent that selectively targets and specifically binds a molecule present on the surface of the targeted cell.La présente invention concerne des compositions et des procédés pour administrer un agent thérapeutique dans le cytoplasme dune cellule. Nous avons développé, entre autres, un système dans lequel deux fragments distincts ou plus - au moins un fragment thérapeutique et au moins un fragment de potentialisation - ciblent sélectivement et se lient spécifiquement à des molécules de surface cellulaire qui sont ensuite internalisées vers un compartiment intracellulaire, lié à la membrane, tel quun endosome. Dans certains modes de réalisation, comme décrit plus avant ci-dessous, un troisi
