The J. David Gladstone Institutes

University of California

Mount Sinai School of Medicine

Deutsches Krebsforschungszentrum

The J. David Gladstone Institutes, a Testamentary Trust Established Under the Will of J. David Gladstone

The J. David Gladstone Institute, a Testamentary Trust Established Under the Will of J. David Gladstone

Melanie Ott

Eric M Verdin

Daniela Boehm

Sara Pagans Lista

Jennifer A Doudna

Ming-Ming Zhou

Aneel K Aggarwal

Andrew S Kondratowicz

Hye-Sook Kwon

Nevan John Krogan

Hyungwook Lim

Priya Shirish Shah

Manfred Jung

Alexander P Doerr

Krystal Ann Fontaine

Parinaz Fozouni

The present disclosure relates to methods using CRISPR-Cas13a enzyme, complexed with HIV or HCV crRNAs to specifically and sensitively detect and quantify the presence of HIV or HCV RNA in a sample. These methods can be used to diagnose HIV or HCV infection, quantify the concentration of HIV or HCV RNA present in a sample, identify the presence of different HIV or HCV splice variants, subtypes, or mutations, and to monitor reactivation of HIV or HCV transcription.

HIV or HCV detection with CRISPR-CAS13A

The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus and/or reducing transcription of HIV integrated into the genome of an HIV-infected cell. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection.

Compositions and methods for reactivating latent immunodeficiency virus

The present disclosure provides methods of treating a flavivirus infection, and compositions for use in the methods.

Compositions and methods for treating Dengue virus infection

The present disclosure provides a method of increasing an immune response in an individual, the method involving administering to an individual in need thereof an inhibitor of SIRT1. The present disclosure provides a method of reducing an immune response, e.g., to treat chronic immune hyperactivity, the method generally involving administering to an individual in need thereof an activator of SIRT1. The present disclosure provides a method of modulating activation and differentiation of CD4T cells.

Use of SIRT1 activators or inhibitors to modulate an immune response

The present invention provides isolated methylated Tat peptides; and compositions comprising the peptides. The present invention further provides isolated antibodies specific for a Lys-51-methylated Tat polypeptide. Also provided are methods of identifying agents that inhibit Lys-51 methylation of a Tat polypeptide. The present invention further provides methods of treating an immunodeficiency virus infection in a mammalian subject.

Screening method for the identification of inhibitors of HIV Tat methylation by the lysine methyltransferase Set7/9

Methylated tat polypeptides and methods of use thereof

The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides binding partners for the bromodomain. The present invention further provides the structural determination of the Tat-P/CAF binding complex determined by NMR spectroscopy. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.

ZA loops of bromodomains

The present invention provides treatment methods involving modulating a sirtuin activity and/or a sirtuin mRNA and/or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and/or SIRT mRNA and/or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and/or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide. The present invention further provides active agents that modulate sirtuin activity or expression; and compositions, including pharmaceutical compositions, comprising the active agents.

Screening methods for the identification of agents that inhibit SIRT1 Tat deacetylase activity

The present invention provides compositions, including immunogenic compositions, comprising acetylated Tat protein of an immunodeficiency virus. The present invention further provides antibodies that specifically bind an acetylated Tat polypeptide. The present invention further provides methods of inducing an immune response to an immunodeficiency virus Tat protein in an individual. The present invention further provides methods of inhibiting transcriptional activation of an immunodeficiency virus in a cell of an individual.

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San Francisco, CA, United States of America

Melanie Ott