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.

公开(公告)号：US11491207B2

公开(公告)日：2022-11-08

申请号：US16397823

申请日：2019-04-29

Applicant: Excision BioTherapeutics, Inc. ,  Temple University of the Commonwealth System of Higher Education

Inventor： Kamel Khalili ,  Thomas Malcolm ,  Kenneth I. Kohn

IPC: A61K38/46 ,  C12Q1/70 ,  C12N15/10 ,  C12N15/00 ,  A61P31/20 ,  A61K39/395 ,  C07K16/28 ,  C12N15/11 ,  A61K48/00 ,  A61K39/00

Abstract: A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.

公开(公告)号：US20220313795A1

公开(公告)日：2022-10-06

申请号：US17329137

申请日：2021-05-24

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：US20210069303A1

公开(公告)日：2021-03-11

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：US20190247470A1

公开(公告)日：2019-08-15

申请号：US16397823

申请日：2019-04-29

Applicant: Excision Bio Therapeutics, Inc. ,  Temple University of the Commonwealth System of Higher Education

Inventor： Kamel Khalili ,  Thomas Malcolm ,  Kenneth I. Kohn

IPC: A61K38/46 ,  A61K48/00 ,  C12N15/11 ,  C07K16/28 ,  A61K39/395 ,  C12Q1/70 ,  A61P31/20 ,  C12N15/10

CPC classification number: A61K38/465 ,  A61K39/39541 ,  A61K48/00 ,  A61K2039/505 ,  A61P31/20 ,  C07K16/2839 ,  C12N15/102 ,  C12N15/11 ,  C12N2310/20 ,  C12Q1/70 ,  Y02A50/467

Abstract: A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.

公开(公告)号：US20190083656A1

公开(公告)日：2019-03-21

申请号：US15768241

申请日：2016-10-14

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

Inventor： Kamel Khalili ,  Thomas Malcolm

IPC: A61K48/00 ,  A61P31/18

Abstract: Compositions include endonucleases of the family Cpf1 (CRISPR from Prevotella and Francisella 1); and at least one guide RNA (gRNA) complementary to a target sequence in a gene to specifically guide the Cpf1 endonuclease to the target site in a host cell in vitro or in vivo. Methods of treating a subject include the use of one or more of these compositions.

公开(公告)号：US20180296649A1

公开(公告)日：2018-10-18

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 ,  A61P31/18 ,  C12N15/11 ,  C12N9/22 ,  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：US09981020B2

公开(公告)日：2018-05-29

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: A61K48/00 ,  A61K38/46 ,  A61K9/00 ,  A61K35/12 ,  A61K45/06 ,  C12N7/00 ,  C12N9/22 ,  C12N15/11 ,  A61K39/21 ,  C12N15/55 ,  C12N15/79 ,  C12N15/85 ,  C12N15/86

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：US20170176408A1

公开(公告)日：2017-06-22

申请号：US15129353

申请日：2015-03-24

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

Inventor： Salim Merali ,  Carlos A. Barrerro ,  Kamel Khalili ,  Jay Rappaport ,  Norman J. Haughey ,  Ned Sacktor

IPC: G01N33/487 ,  G01N30/88

CPC classification number: G01N33/487 ,  G01N30/88 ,  G01N33/5308 ,  G01N2030/8813 ,  G01N2800/2814 ,  G01N2800/52 ,  G01N2800/56

Abstract: Provided is a method of detecting mild neurocognitive disturbance (MNCD) or HIV associated dementia (HAD) in a patient comprising detecting the level of acetyl spermine and/or acetyl spermidine from a cerebrospinal fluid test sample of the patient; and comparing the level of acetyl spermine and/or acetyl spermidine in the test sample to the level of the acetyl spermine and/or acetyl spermidine in a cerebrospinal fluid control sample or to a control value for lack of neurocognitive impairment, MNCD or HAD; wherein an elevated level of acetyl spermine and/or acetyl spermidine in the test sample as compared to the level in the control sample or a control value for lack of neurocognitive impairment, or a level of acetyl spermine and/or acetyl spermidine that is similar to that of a control value for MNCD or HAD, indicates that the patient suffers from MNCD or HAD. Also provided are methods for measuring the progression of an HIV-1-associated neurocognitive disorder, as well as methods for staging such a disorder.

公开(公告)号：US20230193257A1

公开(公告)日：2023-06-22

申请号：US17866261

申请日：2022-07-15

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

Inventor： Kamel Khalili

IPC: C12N15/11 ,  C12N15/113 ,  A61K45/06 ,  A61K48/00 ,  C12N7/00 ,  C12N9/22 ,  C12N15/86

CPC classification number: C12N15/111 ,  C12N15/1132 ,  A61K45/06 ,  A61K48/005 ,  A61K48/0075 ,  C12N7/00 ,  C12N9/22 ,  C12N15/11 ,  C12N15/86 ,  C12N2310/20 ,  C12N2800/107 ,  C12N2830/00 ,  C12N2320/30 ,  C12N2830/30 ,  C12N2310/3519 ,  C12N2740/16062 ,  C12N2800/22 ,  C12N2830/60

Abstract: Compositions and methods are provided for Tat-inducible expression of a CRISPR-associated endonuclease by a truncated HIV LTR promoter containing at least a core region and a TAR region of a HIV LTR promoter. The compositions may be used as a therapeutic treatment for the treatment and/or prevention of HIV.