The present disclosure is directed to methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency. The method of inducing rejuvenation in a population of adult glial progenitor cells may comprise administering, to the population of adult glial progenitor cells, an effective amount of an agent that suppresses one or more transcription factors selected from the group consisting of (i) zinc finger protein 274 (ZNF274), (ii) Myc-associated factor X (MAX), (iii) E2F transcription factor 6 (E2F6), (iv) zinc finger protein Aiolos (IKZF3), and (v) signal transducer and activator of transcription 3 (STAT3).

The present disclosure relates to site-specific disrupting agents for modulating, e.g., decreasing, expression of a target plurality of genes in a cell. In some embodiments, the target plurality of genes comprises pro-inflammatory genes, e.g., CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, and IL-8. In some embodiments, the method comprises using a first site-specific disrupting agent that targets a first anchor sequence and a second site-specific disrupting agents that disrupts a second anchor sequence.

The instant invention provides workflows for the design and characterization of mechanism-based sirtuin modulating compounds, including new or improved sirtuin activating compounds. Workflows for the design of mechanism-based sirtuin activating compounds are provided, based on conditions that must be satisfied by activators if they are to exploit the common catalytic mechanism of all sirtuin enzymes and hence increase catalytic efficiency for any sirtuin and any substrate.

Described herein is a compound selected from the group consisting of AZ960, CYC116, MI-3, Nexturastat A, TAK-901, Tubastatin A hydrochloride salt, and a small interfering RNA molecule comprising any one of SEQ ID No. 5 to SEQ ID No. 28 for use in the treatment of Hepatitis B. The compound may also be used in the manufacture of a medicament for the treatment of Hepatitis B. Also described is a method of treating a Hepatitis B infection in a subject, the method comprises administering to the subject a therapeutically effective dose of the compound as described above.

The present invention relates to Abhydrolase containing domain 5 (ABHD5) and N-terminal fragments of HDAC4 (HDAC4-NT) and variants of the aforementioned peptides for the treatment and prevention of heart failure. The present invention further provides vectors for the cardiomyocyte-specific expression of said peptides and a test system comprising ABHD5 for the identification of novel compounds which are useful for the treatment of heart failure.

Compositions and methods for assessing protein function are provided. A modified SpyCatcher protein that can include a tag is provided. Modified SpyCatcher proteins linked to a protein of interest, such as a nuclease are also provided. The methods include contacting a SpyCatcher protein and a SpyTagged protein to form a complex that may further include a protein of interest, one or more nucleic acids, and/or a nuclease. The methods can be used to purify a protein of interest or identify or target a protein binding site in a nucleic acid.

This disclosure demonstrates that inhibition of Sirt5 can suppress malignant transformation of cells. Therefore, methods of treating cancer based on inhibition of Sirt5 are disclosed.

The instant invention provides workflows for the design and characterization of mechanism-based sirtuin modulating compounds, including new or improved sirtuin activating compounds. Workflows for the design of mechanism-based sirtuin activating compounds are provided, based on conditions that must be satisfied by activators if they are to exploit the common catalytic mechanism of all sirtuin enzymes and hence increase catalytic efficiency for any sirtuin and any substrate.

Methods and compositions are provided for regeneration of retinal neurons and vision restoration after injury, disease, or loss comprising, administration of a nucleic acid sequence encoding Ascl1 and retinal reprogramming potentiating agents, including HDAC inhibitors, STAT-signaling inhibitors and microRNA manipulations in Ascl1-induced retinal regeneration.

Disclosed herein are conditional siRNAs activatable by CBFβ-MYH11 oncogenic gene and use thereof for treating conditions such as acute myeloid leukemia (AML). The conditional siRNAs target MCL-1 or HDAC8.