Abstract: The present application provides methods of treating a CNS disorder (such as glioblastoma and epilepsy) in an individual, comprising systemically (e.g., intravenously or subcutaneously) administering to the individual an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, optionally further comprising administering a second agent (such as an anti-VEGF antibody, a proteasome inhibitor, or an alkylating agent).

Abstract: The present invention relates to methods and compositions for the treatment of hematological malignancy by administering compositions comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug, e.g., sirolimus or a derivative thereof) and an albumin in combination with compositions comprising a second therapeutic agent.

Abstract: The present invention features methods for treating, stabilizing, preventing, and/or delaying cancer by administering nanoparticles that comprise rapamycin or a derivative thereof. The invention also provides compositions (e.g., unit dosage forms) comprising nanoparticles that comprise a carrier protein and rapamycin or a derivative thereof. The invention further provides combination therapy methods of treating cancer comprising administering to an individual an effective amount of nanoparticles that comprise rapamycin or a derivative thereof and a second therapy.

Abstract: The present application provides methods of treating a colon cancer (such as advanced and/or metastatic colon cancer) in an individual, comprising administering to the individual: a) an effective amount of a composition comprising nanoparticles comprising an mTOR inhibitor (such as a limus drug, such as sirolimus or a derivative thereof) and an albumin, b) an effective amount of anti-VEGF antibody (such as bevacizumab), and c) a therapeutically effective FOLFOX regimen (such as FOLFOX4 or a modified FOLFOX6).

Abstract: The present application provides peptides and nucleic acids that are useful for treating virus (e.g., SARS-CoV-2) infection. Exemplary peptides comprise chimeric peptides and blocking peptides that block the interaction between SPIKE and ACE2. Exemplary nucleic acids include siRNAs that specifically target SARS-CoV-2. The present applications also provide complexes and nanoparticles further comprising a second peptide (e.g., a cell-penetrating peptide) that promotes intracellular delivery of the peptides and nucleic acids.

Abstract: The present application provides methods and compositions for treating cancer by administering a composition comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug) and a carrier protein (such as an albumin) based upon the status of one or more mTOR-activating aberration at one or more genes selected from the group consisting of TSC1, TSC2, RPS6, PTEN, TP53, RB1, ATRX, and FAT1.

Abstract: The present invention relates to methods and compositions for the treatment of a solid tumor by administering compositions comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug, e.g., sirolimus or a derivative thereof) and an albumin in combination with compositions comprising a second therapeutic agent.

Abstract: The present invention provides methods of assessing suitability of a pharmaceutical composition for medical use. The pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin.

Abstract: The present invention provides compositions (such as pharmaceutical compositions), and commercial batches of such compositions, comprising nanoparticles comprising albumin and rapamycin. The compositions (such as pharmaceutical compositions) have specific physicochemical characteristics and are particularly suitable for use in treating diseases such as cancer. Also provided are methods of making and methods of using the compositions (such as pharmaceutical compositions).

Abstract: The present application provides guide RNAs and genome-editing complexes or nanoparticles that are useful for specifically targeting a mutated KRAS. Exemplary genome-editing complexes or nanoparticles comprise cell-penetrating peptides, and optionally a DNA nuclease (such as Cas9) or a polynucleotide encoding the DNA nuclease.

Abstract: The present invention provides methods and compositions for treating a hyperplasia (such as cancer, restenosis, or pulmonary hypertension) by administering a composition comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug) and an albumin based upon the status of an mTOR-activating aberration.

Abstract: The present application provides methods and compositions for treating cancer by administering a composition comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug) and a carrier protein (such as an albumin) based upon the mutation status of TSC1 or TSC2 and one of VHL, RBI, PBRIM1, K.DM6A, RET, SETD2 ARID 1 A, BAP1, BRCA2, TP53, RBI, ATRX, FLT1, NTRK1, TLX3, KDM6A, CDH4, CDKN2C, DAXX, ERBB3, GNAS, IL7R, PDGFRB, PMS2, PTEN, SMARCA4, and YY1AP1.

Abstract: The present invention provides compositions (such as pharmaceutical compositions), and commercial batches of such compositions, comprising nanoparticles comprising albumin and rapamycin. The compositions (such as pharmaceutical compositions) have specific physicochemical characteristics and are particularly suitable for use in treating diseases such as cancer. Also provided are methods of making and methods of using the compositions (such as pharmaceutical compositions).

Abstract: The present application is directed to cargo delivery complexes for intracellular delivery of a cargo molecule comprising: a first peptide comprising a cell-penetrating peptide (CPP), a second peptide comprising a cell-penetrating peptide, and a cargo molecule. The second peptide comprises a polyethylene glycol (PEG) moiety linked to the second CPP, and the first peptide does not have a PEG moiety. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the CPP is a retro-inverso peptide. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the peptide further comprises a targeting sequence selected from the group consisting of GYVSK, GYVS, YIGS and YIGSR. Methods of making and using the cargo delivery complexes are also disclosed.

Abstract: The present invention provides methods of assessing suitability of a pharmaceutical composition for medical use. The pharmaceutical composition comprises nanoparticles comprising rapamycin coated with albumin and a non-nanoparticle portion comprising albumin and rapamycin.

Abstract: The present invention provides compositions and devices for subcutaneously administering compositions comprising nanoparticles comprising an mTOR inhibitor and an albumin. The present application also provides methods of treating diseases by subcutaneously administering to an individual a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin.

Abstract: The present invention features methods for treating, stabilizing, preventing, and/or delaying cancer by administering nanoparticles that comprise rapamycin or a derivative thereof. The invention also provides compositions (e.g., unit dosage forms) comprising nanoparticles that comprise a carrier protein and rapamycin or a derivative thereof. The invention further provides combination therapy methods of treating cancer comprising administering to an individual an effective amount of nanoparticles that comprise rapamycin or a derivative thereof and a second therapy.

Abstract: The present invention provides methods and compositions for treating epithelioid cell tumors (such as a PEComa) by administering a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin.

Abstract: The present invention features methods for treating, stabilizing, preventing, and/or delaying pulmonary hypertension by administering nanoparticles that comprise rapamycin or a derivative thereof and/or nanoparticles that comprise a taxane (e.g., paclitaxel) or a derivative thereof. The invention also provides compositions (e.g., unit dosage forms) comprising nanoparticles that comprise a carrier protein and rapamycin or a derivative thereof and/or nanoparticles that comprise a carrier protein and a taxane (e.g., paclitaxel) or a derivative4 thereof.

Abstract: The present application provides methods and compositions for treating cancer by administering a composition comprising nanoparticles that comprise an mTOR inhibitor (such as a limus drug) and a carrier protein (such as an albumin) based upon the status of one or more mTOR-activating aberration at one or more genes selected from the group consisting of TSC1, TSC2, RPS6, PTEN, TP53, RB1, ATRX, and FAT1.