公开(公告)号：US20230220361A1

公开(公告)日：2023-07-13

申请号：US17817781

申请日：2022-08-05

申请人： TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

发明人： Rafal KAMINSKI ,  Tricia BURDO

IPC分类号： C12N9/22 ,  C12N15/86 ,  A61P31/18

CPC分类号： C12N9/22 ,  C12N15/86 ,  A61P31/18 ,  C12N2310/20

摘要： Migration of HIV-1 infected monocytes across the endothelial barrier plays an essential role in establishing and maintenance of viral reservoir in the brain and leads to neuroinflammation, neuronal damage, and subsequent HIV-induced central nervous system (CNS) dysfunction. These processes continue despite antiretroviral therapy (ART) due to limited pharmacological permeability of the blood-brain barrier, the presence of residual viral replication, and the reactivation of latent viruses. Compositions comprising Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonucleases targeted to activated leukocytes cell adhesion molecule (ALCAM/CD166), chemotactic recruitment (CCR2/5), adhesion to the endothelium (ALCAM) and junctional diapedesis (JAM-A) achieves maximum repression of leukocyte transmigration and block of the spread of the virus to different tissues and organs.

公开(公告)号：US20240336939A1

公开(公告)日：2024-10-10

申请号：US18566446

申请日：2022-06-02

申请人： TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

发明人： Kamel KHALILI ,  Rafal KAMINSKI

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N15/11

CPC分类号： C12N15/907 ,  C12N9/22 ,  C12N15/11

摘要： Compositions include CRISPR-associated endonuclease, and one or more isolated nucleic acid sequences encoding gRNAs, wherein each gRNA is complementary to a target sequence in a retroviral genome. At least one endonuclease targets a Mannosyl Oligosaccharide Glucosidase (MOGS).

公开(公告)号：US20240261436A1

公开(公告)日：2024-08-08

申请号：US18566468

申请日：2022-06-02

申请人： TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

发明人： Kamel KHALILI ,  Rafal KAMINSKI

IPC分类号： A61K48/00 ,  A61K31/4985 ,  A61K31/505 ,  A61K31/52 ,  A61K31/7068 ,  A61P31/18 ,  C12N9/22 ,  C12N15/113

CPC分类号： A61K48/005 ,  A61K31/4985 ,  A61K31/505 ,  A61K31/52 ,  A61K31/7068 ,  A61P31/18 ,  C12N9/22 ,  C12N15/1132 ,  C12N15/1138 ,  C12N2310/20

摘要： Compositions for specifically cleaving target sequences in retroviruses include nucleic acids encoding a Clustered Regularly Interspace Short Palindromic Repeat (CRISPR) associated endonuclease and a guide RNA sequence complementary to a target sequence in a retrovirus and a receptor used by a retrovirus for infecting a cell. The CRISPR construct edits, for example, proviral HIV DNA, thereby eliminating the provirus from an infected cell and simultaneously edits a viral receptor, e.g. CCR5 preventing infection and reinfection of the host.