公开(公告)号：US20180228876A1

公开(公告)日：2018-08-16

申请号：US15950236

申请日：2018-04-11

Applicant: Temple University of the Commonwealth System of Higher Education

Inventor： Kamel Khalili ,  Wenhui Hu

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

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：US09925248B2

公开(公告)日：2018-03-27

申请号：US14838057

申请日：2014-08-29

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：US20160017301A1

公开(公告)日：2016-01-21

申请号：US14838057

申请日：2014-08-29

Applicant: TEMPLE UNIVERSITY OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Kamel Khalili ,  Wenhui Hu

IPC: C12N9/22 ,  C12N7/00 ,  A61K48/00 ,  A61K35/12 ,  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 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.

Abstract translation: 通过用包含聚集的定期间隔短回文序列（CRISPR）相关内切核酸酶的组合物和两种或更多种不同的引导RNA来处理宿主细胞，使整合到潜伏感染逆转录病毒的宿主细胞基因组中的前病毒DNA失活的方法 （gRNA），其中所述至少两个gRNA中的每一个与前病毒DNA中的长末端重复（LTR）中的不同靶核酸序列互补，并使前病毒DNA失活。 用于灭活整合到潜伏感染逆转录病毒的宿主细胞的基因组中的前病毒DNA的组合物，包括分离的包含CRISPR相关内切核酸酶和引导RNA的核酸序列，其中所述指导RNA与 人类免疫缺陷病毒。

公开(公告)号：US11285193B2

公开(公告)日：2022-03-29

申请号：US15882207

申请日：2018-01-29

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 treating a subject at risk for having a virus infection, by administering to the subject a prophylactically 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 virus, and preventing a retroviral infection.

公开(公告)号：US11273209B2

公开(公告)日：2022-03-15

申请号：US16875271

申请日：2020-05-15

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：US20180221458A1

公开(公告)日：2018-08-09

申请号：US15942773

申请日：2018-04-02

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 or at risk for having an HIV-1 virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a 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 completely resolving the symptoms of HIV-1, decreasing the severity of the symptoms of HIV-1, or slowing HIV-1's progression.