Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.

Provided are methods for the treatment of insulin resistance and insulin receptor diseases with SHP2 inhibitors, such as allosteric inhibitors of SHP2 and RNAi or siRNA that target SHP2 expression. Compositions and methods for delivery of SHP2 inhibitors, such as liver-targeting liposomes or nanoparticles, are also provided.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Various embodiments of the present invention are directed to the field of Oncology, and in particular, embodiments directed to a method of ameliorating, treating, or preventing a malignancy in a human subject wherein the steps of the method assist or boost the immune system in eradicating cancerous cells. Certain embodiments are directed to the field of human longevity and aging in a manner such that cancer is not contracted due to ameliorating, treating, or reducing aging by increasing the healthspan and lifespan of humans. In certain embodiments, administration of beneficial bacteria to an individual's microbiome that have been modified so as to produce effective amounts of desired compositions, compounds, agents, e.g. tomatidine, rapamycin, p53 protein, statins, etc., is employed to treat and prevent cancer and other age-related diseases.

A novel peptide sequence that is a modified derivative of a neuron-specific tyrosine phosphatase is shown and described. Specifically, the novel peptide sequence is a modified derivative of striatal-enriched tyrosine phosphatase (STEP). The peptide sequence has been modified so as to be able to ameliorate and treat brain injury resulting from excessive glutamate release and/or oxidative stress. Examples of the types of brain injury which the presently disclosed peptide sequence is useful for treating includes acute brain injury resulting from stroke or traumatic brain injury and chronic disorders such as Huntington's chorea and schizophrenia. Furthermore, the presently described peptide sequence may further be useful in the treatment and amelioration of disorders associated with fear memory such as post-traumatic stress disorder.

The present disclosure provides antigen presenting polypeptide comprising a TGF-? MOD that is reversibly masked and acts as a TGF-? receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, Type 1 Diabetes (T1D) associated epitope containing polypeptides. The antigen-presenting polypeptides and their T1D-associated epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of T1D.

Described herein are compositions and methods for the prevention or treatment of osteoarthritis by administrating a therapeutically effective amount of at least one SHP2 antagonistic agent to the subject. The SHP2 antagonistic agent can be a SHP2 inhibitor, a PROTAC degrader of SHP2 proteins, and/or a SHP2 RNA interference or a small interfering RNA, or a combination thereof.

The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. In particular, the new receptors contain a heterologous stop-transfer-sequence and a ?-secretase cleavable transmembrane domain. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers.