The invention relates to compositions of vault complexes containing recombinant cytokine fusion proteins that include a cytokine and a vault targeting domain, and methods of using the vault complexes to deliver the cytokines to a cell or subject, and methods for using the compositions to treat cancer, such as lung cancer.

The present invention relates to methods of treating a condition associated with mTORC1 hyperactivation or TSC2-deficient cancer, the method comprising administering to a subject having the cancer a pharmaceutically-effective amount of a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor. In some embodiments, the condition associated with mTORC1 hyperactivation is tuberous sclerosis complex (TSC). In some embodiments, the condition associated with mTORC1 hyperactivation is lymphangioleiomyomatosis (LAM). In some embodiments, the condition associated with mTORC1 hyperactivation is TSC2-deficient cancer.

Described herein are compositions and methods for the immobilization of passenger molecules in a dense matrix of ADP-ribose within the vault particle. The present disclosure also describes a method for altering the physicomechanical properties (e.g. density, compressive strength, electrostatic properties, etc.) of packaged vaults for enhanced stability and/or downstream functionality. In addition, the present disclosure also describes compositions and methods for altering amino acid sequence of the vault protein in the vault particle by amino acid mutation, amino acid insertion and/or amino acid deletion to package passenger molecules and/or to target vault particles to specific receptors or ligands.

Compounds for treatment of diseases having acidic or hypoxic diseased tissues and pharmaceutical compositions comprising the compounds, as well as methods for making and using the compounds and compositions.

A non-naturally occurring peptide linker, comprising a site-specific conjugation motif of GGX.sub.1X.sub.2Q, which allows for site-specific conjugation mediated by a transglutaminase; wherein each of X.sub.1 and X.sub.2 independently represents any naturally-occurring amino acid or one of X.sub.1 and X.sub.2 is absent; and wherein the non-naturally occurring peptide has a length of 9-20 amino acids. Also provided herein are fusion polypeptides such as tandem single-domain multi-specific antibodies containing such peptide linkers.