公开(公告)号：US11298410B2

公开(公告)日：2022-04-12

申请号：US15578372

申请日：2016-06-01

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：US20190085326A1

公开(公告)日：2019-03-21

申请号：US16208314

申请日：2018-12-03

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

Inventor： Kamel Khalili ,  Wenhui Hu ,  Rafal Kaminski ,  Thomas Malcolm

IPC: C12N15/11 ,  C12N9/22 ,  A61P31/18 ,  A61K9/00 ,  A61K45/06 ,  A61K31/7088 ,  A61K38/46

Abstract: A CRISPR-endonuclease gene editing composition includes a guide RNA (gRNA) for targeting a specific viral sequence for cleavage by the endonuclease which introduces breaks in the double stranded DNA identified by the gRNA. Placing the gene encoding Cas9 under the control of a minimal promoter of, for example, HIV spanning the 5′-LTR, results in the activation by the HIV-1 transactivator protein, Tat. Co-expression of both a multiplex of, for example, HIV-specific gRNAs and endonuclease, e.g. Cas9, in cells results in the modification and/or excision of the segment of viral DNA, leading to the eradication of the virus in vitro and in vivo.

公开(公告)号：US20180236044A1

公开(公告)日：2018-08-23

申请号：US15885936

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 personalized method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus, by determining a nucleic acid sequence of the proviral DNA harbored by a subject, designing two or more different guide RNAs (gRNAs) complementary to the proviral DNA sequences in the subject, treating the subject'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 inactivating the proviral DNA.

公开(公告)号：US12122997B2

公开(公告)日：2024-10-22

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 ,  A61K48/00 ,  C12N9/22 ,  C12N15/113

CPC classification number: C12N15/11 ,  A61K48/00 ,  C12N9/22 ,  C12N15/1132 ,  A01K2227/105 ,  A01K2267/0337 ,  C07K2319/09 ,  C12N2310/20 ,  C12N2750/14143

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：US11291710B2

公开(公告)日：2022-04-05

申请号：US16874295

申请日：2020-05-14

Applicant: Temple University of The Commonwealth System of Higher Education

Inventor： Kamel Khalili ,  Wenhui Hu

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

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：US20180214521A1

公开(公告)日：2018-08-02

申请号：US15939710

申请日：2018-03-29

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: A method of immunizing a subject at risk of HIV-1 virus infection, by administering to the subject a prophylactically effective amount of 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 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 HIV-1 virus infection in the subject.

公开(公告)号：US20180169194A1

公开(公告)日：2018-06-21

申请号：US15884427

申请日：2018-01-31

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: A method of treating a subject having a retroviral infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5′- to 3′-LTRs of the sequence in the retrovirus, and eradicating the retroviral infection. A method of immunizing a subject at risk of retroviral infection, by administering a prophylactically effective amount of 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 proviral DNA of a retrovirus to the subject, and preventing retroviral infection in the subject.

公开(公告)号：US20180073018A1

公开(公告)日：2018-03-15

申请号：US15705825

申请日：2017-09-15

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

Inventor： Wenhui Hu ,  Kamel Khalili ,  Yonggang Zhang

IPC: C12N15/11 ,  A61K48/00 ,  C12N7/00 ,  C12N9/22 ,  C12N15/113 ,  C07K14/005

CPC classification number: C12N15/11 ,  A61K39/21 ,  A61K48/005 ,  C07K14/005 ,  C07K2319/71 ,  C12N7/00 ,  C12N9/22 ,  C12N15/1132 ,  C12N2310/16 ,  C12N2310/20 ,  C12N2310/3519 ,  C12N2740/16022 ,  C12N2740/16051 ,  C12N2740/16062 ,  C12N2795/18122 ,  C12N2795/18133 ,  C12N2800/40

Abstract: The present invention relates to compositions and methods for reactivation of HIV in vivo or in vitro. latently infected cell. In one embodiment, the present invention uses the CRISPR/Cas9 system in combination with the MS2 bacteriophage coat protein-mediated synergistic activation mediator (SAM) system to provide enhanced transcriptional activation of the HIV genome.

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：US20230001016A1

公开(公告)日：2023-01-05

申请号：US17727438

申请日：2022-04-22

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

Inventor： Kamel Khalili ,  Wenhui Hu ,  Hassen Wollebo

IPC: A61K48/00 ,  C12N9/22 ,  C12N15/63 ,  C12N15/113

Abstract: The present invention includes methods and compositions for elimination of polyomaviruses, such as John Cunningham Virus (JVC), from host cells, and the treatment of polyomavirus related diseases, such as progressive multifocal leukoencephalopathy (PML). The compositions include isolated nucleic acid sequences comprising an CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a polyomavirus.