公开(公告)号：US20250135032A1

公开(公告)日：2025-05-01

申请号：US18834040

申请日：2023-01-30

Applicant: TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Kamel KHALILI ,  Chen CHEN ,  Shuren LIAO ,  Hong LIU

IPC: A61K48/00 ,  A61K38/46 ,  C12N15/11 ,  C12N15/86 ,  C12Q1/6883

Abstract: Compositions include gene-editing complexes for the treatment of myopathies, cancer and neurodegenerative diseases. Specifically, the disclosure provides methods of identifying in a subject's biological sample, ‘at least one Bcl2-associated anthanogene 3 (BAGS) genetic mutation as compared to a control BAGS nucleic acid sequence, and administering to the subject a therapeutically effective amount of a gene-editing complex, wherein the gene-editing complex corrects the bag3 mutation to a wild-type bag3, thereby, treating the subject.

公开(公告)号：US20180200343A1

公开(公告)日：2018-07-19

申请号：US15902263

申请日：2018-02-22

Applicant: Temple University of the Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui HU

IPC: A61K38/46 ,  C12N7/00 ,  A61K9/00 ,  A61K35/12 ,  A61K45/06 ,  C12N15/11 ,  C12N9/22 ,  A61K48/00

CPC classification number: A61K38/465 ,  A61K9/0034 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  A61K48/005 ,  C12N7/00 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/20 ,  C12N2320/30 ,  C12N2740/16063 ,  C12Y301/21

Abstract: A method of treating a subject having or at risk for having a virus infection, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the virus, and completely excising a fragment of greater than 9000-bp of integrated proviral DNA that spanned from its 5′- to 3′-LTRs. A method of treating a subject having or at risk for having a genetic caused disease, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the sequence of the subjects DNA greater than 9000-bp that is chromosomally integrated and causes the genetic caused disease, and excising the chromosomally integrated sequence.

公开(公告)号：US20180169193A1

公开(公告)日：2018-06-21

申请号：US15879877

申请日：2018-01-25

Applicant: Temple University of the Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui HU

IPC: A61K38/46 ,  C12N15/11 ,  A61K35/12 ,  A61K48/00 ,  C12N7/00 ,  C12N9/22 ,  A61K9/00 ,  A61K45/06

CPC classification number: A61K38/465 ,  A61K9/0034 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  A61K48/005 ,  C12N7/00 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/20 ,  C12N2320/30 ,  C12N2740/16063 ,  C12Y301/21

Abstract: Methods of inactivating a proviral DNA genome or a DNA genome integrated into the genome of a host cell latently infected with a retrovirus, by treating the host cell with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the proviral DNA that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire proviral genome of the proviral DNA, and eradicating the proviral DNA from the host cell.

公开(公告)号：US20160250300A1

公开(公告)日：2016-09-01

申请号：US15148261

申请日：2016-05-06

Applicant: TEMPLE UNIVERSITY OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Kamel KHALILI ,  Wenhui HU

IPC: A61K38/46

CPC classification number: A61K38/465 ,  A61K9/0034 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  A61K48/005 ,  C12N7/00 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/20 ,  C12N2320/30 ,  C12N2740/16063 ,  C12Y301/21

Abstract: A method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus by treating the host cell with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) in the proviral DNA, and inactivating the proviral DNA. A composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including isolated nucleic acid sequences comprising a CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a human immunodeficiency virus.

公开(公告)号：US20240336939A1

公开(公告)日：2024-10-10

申请号：US18566446

申请日：2022-06-02

Applicant: TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Kamel KHALILI ,  Rafal KAMINSKI

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

CPC classification number: C12N15/907 ,  C12N9/22 ,  C12N15/11

Abstract: 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

Applicant: TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Kamel KHALILI ,  Rafal KAMINSKI

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

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

Abstract: 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.

公开(公告)号：US20240139294A1

公开(公告)日：2024-05-02

申请号：US18298913

申请日：2023-04-11

Applicant: Temple University - of the Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui Hu

IPC: A61K38/46 ,  A61K9/00 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  C12N7/00 ,  C12N9/22 ,  C12N15/11

CPC classification number: A61K38/465 ,  A61K9/0034 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  A61K48/005 ,  C12N7/00 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/20 ,  C12N2320/30 ,  C12N2740/16063 ,  C12Y301/21

Abstract: A method of preventing transmission of a retrovirus from a mother to her offspring, by administering to the mother a therapeutically effective amount of a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and the two or more different multiplex gRNAs, wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, eradicating the HIV-1 proviral DNA from the host cell, and preventing transmission of the proviral DNA to the offspring.

公开(公告)号：US20190225963A1

公开(公告)日：2019-07-25

申请号：US15998558

申请日：2017-02-13

Applicant: Temple University - Of The Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui HU

IPC: C12N15/11 ,  C12N9/22

Abstract: Compositions for the in vivo delivery of a gene editing CRISPR/Cas9 complex was developed to eliminate integrated retroviral DNA sequences from latently infected human cells and animal disease models

公开(公告)号：US20210052709A1

公开(公告)日：2021-02-25

申请号：US17017037

申请日：2020-09-10

Applicant: Temple University - of the Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui HU ,  Yonggang ZHANG

IPC: A61K38/46 ,  C12N15/113 ,  A61K48/00 ,  A61P31/18 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90

Abstract: 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 one or more target nucleic acid sequences in a retrovirus genome.

公开(公告)号：US20180236045A1

公开(公告)日：2018-08-23

申请号：US15885940

申请日：2018-02-01

Applicant: Temple University of the Commonwealth System of Higher Education

Inventor： Kamel KHALILI ,  Wenhui HU

IPC: A61K38/46 ,  C12N7/00 ,  A61K9/00 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  C12N9/22 ,  C12N15/11

CPC classification number: A61K38/465 ,  A61K9/0034 ,  A61K35/12 ,  A61K45/06 ,  A61K48/00 ,  A61K48/005 ,  C12N7/00 ,  C12N9/22 ,  C12N15/111 ,  C12N2310/20 ,  C12N2320/30 ,  C12N2740/16063 ,  C12Y301/21

Abstract: A method of preventing transmission of a retrovirus from a mother to her offspring, by treating the mother's host cells with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the proviral DNA, and preventing transmission of the proviral DNA to the offspring.