公开(公告)号：US20160324989A1

公开(公告)日：2016-11-10

申请号：US15110211

申请日：2015-01-13

Applicant: WAKE FOREST UNIVERSITY HEALTH SCIENCES

Inventor： King C. Li ,  Akiva Mintz ,  Xiaobing Xiong ,  Youngkyoo Jung ,  Yao Sun

IPC: A61K48/00 ,  A61K45/06 ,  A61K38/19 ,  A61K38/18 ,  C07K14/525 ,  A61M37/00 ,  C07K14/49 ,  A61K35/30 ,  C07K14/52 ,  A61K9/00 ,  A61K41/00 ,  C12N15/86 ,  A61K35/28 ,  C07K14/495

CPC classification number: A61K48/0083 ,  A61K9/0019 ,  A61K35/28 ,  A61K35/30 ,  A61K35/545 ,  A61K38/1841 ,  A61K38/1866 ,  A61K38/19 ,  A61K38/191 ,  A61K41/0047 ,  A61K45/06 ,  A61K48/005 ,  A61K48/0058 ,  A61K48/0066 ,  A61M37/0092 ,  A61P35/00 ,  C07K14/49 ,  C07K14/495 ,  C07K14/52 ,  C07K14/525 ,  C12N15/86 ,  C12N2830/002

Abstract: A method of increasing blood-brain barrier permeability of selected brain tissue in a subject in need thereof is carried out by: (a) parenterally administering to the subject stem cells that migrate to the brain tissue, the stem cells containing a recombinant nucleic acid, the recombinant nucleic acid comprising a nucleic acid encoding a barrier-opening protein or peptide operably associated with a heat-inducible promoter; and then (b) selectively heating the selected brain tissue sufficient to induce the expression of the barrier-opening protein or peptide in an amount effective to increase the permeability of the blood-brain barrier in the selected brain tissue. Nucleic acids, vectors, stem cells and compositions useful for carrying out such methods are also described.

Abstract translation: 通过以下方法进行选择性脑组织中选择的脑组织的血脑屏障通透性的方法：（a）胃肠外给予迁移至脑组织的干细胞，含有重组核酸的干细胞， 所述重组核酸包含编码与热诱导型启动子可操作地相关联的阻断开启蛋白或肽的核酸; 然后（b）选择性地加热所选择的脑组织足以诱导阻断开启蛋白或肽的表达，其量可以有效增加所选择的脑组织中血脑屏障的通透性。 还描述了用于实施这些方法的核酸，载体，干细胞和组合物。