公开(公告)号：US20180236046A1

公开(公告)日：2018-08-23

申请号：US15885942

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 composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including an isolated nucleic acid encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, an isolated nucleic acid sequence encoding a first guide RNA (gRNA) having a first spacer sequence that is complementary to a first target protospacer sequence in a proviral DNA, and an isolated nucleic acid sequence encoding a second gRNA having a second spacer sequence that is complementary to a second target protospacer sequence in the proviral DNA, wherein said first target protospacer sequence and said second target protospacer sequence are situated in a long terminal repeat (LTR) of the proviral DNA. A pharmaceutical composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus.

公开(公告)号：US20180228874A1

公开(公告)日：2018-08-16

申请号：US15904730

申请日：2018-02-26

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 pharmaceutical composition for use in inactivating an HIV-1 proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including 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 HIV-1 proviral DNA, whereby treating the host cell with the composition cleaves a double strand of the HIV-1 proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease and cleaves a double strand of the HIV-1 proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease and thereby excises an entire HIV-1 proviral genome and eradicates the HIV-1 proviral DNA from the host cell, and a pharmaceutically acceptable carrier.

公开(公告)号：US20180207243A1

公开(公告)日：2018-07-26

申请号：US15921731

申请日：2018-03-15

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 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 causing neither genotoxicity nor off-target editing to the host.

公开(公告)号：US20170016066A1

公开(公告)日：2017-01-19

申请号：US15115807

申请日：2015-01-30

Applicant: TEMPLE UNIVERSITY OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Inventor： Arthur M. FELDMAN ,  Douglas G. TILLEY ,  Weizhong ZHU ,  Kamel KHALILI ,  Walter J. KOCH

IPC: C12Q1/68 ,  G01N33/68

CPC classification number: C12Q1/6883 ,  A61K48/00 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/6887 ,  G01N33/6893 ,  G01N2500/04 ,  G01N2500/10 ,  G01N2800/325 ,  G01N2800/50

Abstract: Compositions are directed to BCL2-associated athanogene 3 (BAG3) molecules and agents which modulate expression of BAG3 molecules. Pharmaceutical composition for administration to patients, for example, patients with heart failure, comprise one or more BAG3 molecules or agents which modulate expression of BAG3. Methods of treatment and identifying candidate therapeutic agents are also provided.

Abstract translation: 组合物针对BCL2相关的athanogene 3（BAG3）分子和调节BAG3分子表达的试剂。 用于给予患者的药物组合物，例如患有心力衰竭的患者，包含调节BAG3表达的一种或多种BAG3分子或试剂。 还提供了治疗和鉴定候选治疗剂的方法。