The present invention provides novel neurotoxins and compositions comprising the same. The neurotoxins are useful in therapy, particularly for preventing, regulating or reducing neuropathic pain or sweating. Methods and kits for producing the neurotoxins are also provided.

The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

The present disclosure relates generally to methods and compositions for modulating frataxin (FXN) expression, e.g., to treat Friedreich ataxia (FRDA).

The present disclosure provides synthetic collagen and methods of making and using synthetic collagen that include a synthetic collagen that facilitates wound closure comprising an isolated and purified triple helical backbone protein that facilitates wound closure comprising one or more alteration in a triple helical backbone protein sequence, that stabilize the isolated and purified triple helical backbone protein and does not disrupt an additional collagen ligand interaction; and one or more integrin binding motifs, wherein the isolated and purified triple helical backbone protein facilitates wound closure.

A trigger-responsive immune-inactivating signaling polypeptide disclosed herein can include a modulating domain and an immune-inactivating moiety, such as a dominant negative signaling moiety or constitutively active signaling moiety. A modulating domain can be characterized by an ability to adopt a first state and a second state, and to transition between the first state and the second state when exposed to a trigger. When the modulating domain is in its first state, the immune-inactivating signaling moiety can be inhibited, and when the modulating domain is in its second state, the inhibition can be relieved. Further disclosed herein are compositions for the delivery of a trigger-responsive immune-inactivating signaling polypeptide. Also, methods for using a trigger-responsive immune-inactivating signaling polypeptide, including to regulate an activity of immune system cells, are disclosed.

Disclosed herein are conjugates including a fatty acid, a self-assembly domain, and a polypeptide, where the conjugates have phase transition behavior. Further disclosed are methods of using the conjugates to treat disease, methods of delivering an agent, and methods of preparing the conjugates.

The present disclosure provides compositions and methods for treating or preventing ulcers in subjects having low red blood cell levels and/or hemoglobin levels (e.g, anemia). In some embodiments, the compositions of the disclosure may be used to treat or prevent ulcers associated with anemia.

A proprotein containing a functional protein coupled to a peptide mask that inhibits binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask.

The invention features nucleic acid constructs encoding chimeric immune T-cell receptors (CIRs) that are useful for treating HIV in patients. In general, the CIRs contain an extracellular domain which targets HIV or HIV infected cells (e.g., the extracellular domain of CD4), a transmembrane domain, and a cytoplasmic domain for mediating T-cell activation (e.g., CD3 zeta and/or the partial extracellular domain of CD28). The invention also features the use of host cells expressing CIRs in the treatment of HIV.

The present invention provides an isolated methyl degron peptide and a fusion protein comprising a methyl degron peptide. Also, the present invention provides screening methods for agents affecting protein lifespan and anti-cancer agents. Moreover, the present invention provides methods of controlling protein lifespan, regulating protein expression, and treating cancers by using a methyl degron peptide or a methyl degron gene.