Patents Assigned to Temple University of the Commonwealth System of Higher Education
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Publication number: 20180236043Abstract: A method of treating a subject having or at risk for having a virus 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 virus. A method of treating a subject having or at risk for having a virus 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 virus, and causing neither genotoxicity nor off-target editing to the host.Type: ApplicationFiled: January 29, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180236046Abstract: 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.Type: ApplicationFiled: February 1, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180236041Abstract: 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.Type: ApplicationFiled: January 29, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180236044Abstract: 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.Type: ApplicationFiled: February 1, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui Hu
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Publication number: 20180236045Abstract: 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.Type: ApplicationFiled: February 1, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180236042Abstract: 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.Type: ApplicationFiled: January 29, 2018Publication date: August 23, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Patent number: 10054583Abstract: Compositions include nucleic acid sequences encoding the C-terminal fragment of fragment (Seg3) of Nuclear factor-erythroid 2 related factor 2 (Nrf2). These compositions provide a target for identification of novel therapeutics having the ability to modulate the translation of Nrf2. Methods of treating subjects are also provided.Type: GrantFiled: October 9, 2013Date of Patent: August 21, 2018Assignee: TEMPLE UNIVERSITY OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATIONInventors: Oscar M. Perez-Leal, Salim Merali, Carlos A. Barrero
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Publication number: 20180228876Abstract: 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.Type: ApplicationFiled: April 11, 2018Publication date: August 16, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel Khalili, Wenhui Hu
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Publication number: 20180228874Abstract: 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.Type: ApplicationFiled: February 26, 2018Publication date: August 16, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180214521Abstract: 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.Type: ApplicationFiled: March 29, 2018Publication date: August 2, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel Khalili, Wenhui Hu
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Publication number: 20180207243Abstract: 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.Type: ApplicationFiled: March 15, 2018Publication date: July 26, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180200343Abstract: 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.Type: ApplicationFiled: February 22, 2018Publication date: July 19, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180169193Abstract: 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.Type: ApplicationFiled: January 25, 2018Publication date: June 21, 2018Applicant: Temple University of the Commonwealth System of Higher EducationInventors: Kamel KHALILI, Wenhui HU
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Publication number: 20180169194Abstract: 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.Type: ApplicationFiled: January 31, 2018Publication date: June 21, 2018Applicant: Temple University of the Commonwealth system of Higher EducationInventors: Kamel KHALILI, Wenhui Hu
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Patent number: 9981020Abstract: 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.Type: GrantFiled: May 6, 2016Date of Patent: May 29, 2018Assignee: Temple University of the Commonwealth System of Higher EducationInventors: Kamel Khalili, Wenhui Hu
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Publication number: 20180140682Abstract: 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.Type: ApplicationFiled: January 8, 2018Publication date: May 24, 2018Applicants: Excision BioTherapeutics, Inc., Temple University of the Commonwealth System of Higher EducationInventors: Kamel Khalili, Thomas Malcolm, Kenneth I. Kohn
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Patent number: 9975879Abstract: Pharmaceutical compositions of the invention comprise compounds, compositions, methods useful for the treatment of drug addiction, drug withdrawal, and diseases or conditions that involve dysregulation of glutamate homeostasis in it etiology.Type: GrantFiled: June 4, 2014Date of Patent: May 22, 2018Assignee: Temple University of the Commonwealth System of Higher EducationInventors: Magid Abou-Gharbia, Wayne E. Childers, Rogelio L. Martinez, Mercy M. Ramanjulu, Benjamin E. Blass
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Patent number: 9933435Abstract: Provided is a method for diagnosing and/or staging COPD based on detection of one or more histone proteins. In some embodiments, the histone protein is an H3.3 protein comprising a post-translational modification. In some embodiments, the histone protein is H2B, H3, H3.3 or H4. Kits for practicing the methods of diagnosis and/or staging are provided as well. Further provided is a method for treating COPD.Type: GrantFiled: February 16, 2016Date of Patent: April 3, 2018Assignee: TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATIONInventors: Salim Merali, Camilo Moncada, Steven G. Kelsen, Carlos A. Barrero, Oscar Mauricio Perez Leal
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Patent number: 9925248Abstract: 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.Type: GrantFiled: August 29, 2014Date of Patent: March 27, 2018Assignee: TEMPLE UNIVERSITY OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATIONInventors: Kamel Khalili, Wenhui Hu
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Patent number: 9903871Abstract: An embodiment of the invention relates to the use of stabilized cancer peptide fragments derived from “redoxin proteins” selected from the group consisting of thioredoxin; peroxiredoxin-1, 2 and 3; glutaredoxin-3; glutathione peroxidase-4; and nucleoredoxins for the diagnosis of cancers, particularly pancreatic cancer. A method for the detection of cancer, severity of cancer, and/or effectiveness of a therapeutic regimen comprises detecting and/or measuring the amount of redoxin peptide fragments present in the biological sample of a subject.Type: GrantFiled: July 15, 2015Date of Patent: February 27, 2018Assignee: Temple University of the Commonwealth System of Higher EducationInventors: Frank N. Chang, George P. Tuszynski