Abstract: Biodegradable cationic polyesters for intramuscular delivery of nucleic acids, including self-amplifying mRNA, and methods of their use for treating conditions or diseases are disclosed.

Abstract: Nanocarriers are engineered to realize the potential of RNA therapeutics. This work reports the design of pho-to-crosslinked bioreducible nanoparticles (XbNPs) for stable siRNA encapsulation in high serum conditions, shielded surface charge, efficient intracellular trafficking, and triggered cytosolic RNA release. These attributes of XbNPs leads to robust siRNA-mediated knockdown in cancer cells and potent systemic siRNA delivery to tumors in the lungs.

Abstract: Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed. More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVTh?F, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.

Abstract: The disclosure is directed to a biodegradable particle comprising a polyester or polyester blend, a first protein that binds to an immune cell, and a second protein that promotes proliferation and/or activation of immune cells, and a third soluble protein or small molecule encapsulated within the particle. The second protein is a fusion protein comprising at least a portion of an antibody and at least a portion of a cytokine (i.e., an immunocytokine). The disclosure also is directed to methods for treating a disease or condition in a subject (e.g., an autoimmune disease) comprising administering the aforementioned biodegradable particle to the subject.

Abstract: Compositions comprising degradable polymers combined with nucleic acids, such as DNA and RNA, encoding antigen and their use as genetic vaccines are disclosed.

Abstract: The present invention provides biodegradable, biomimetic particles for interacting with cells, including immune cells. In various embodiments, the particles comprise a polymer blend comprising a polyester, such as poly(lactic-co-glycolic acid) (PLGA) and a polyamine, such as poly(beta-amino ester) (PBAE). The particles further comprise, on their surface, one or more ligands for one or more cell surface receptor(s) or cell surface molecule(s). In some embodiments, the cell surface receptor or cell surface molecule is on an immune cell, such as a lymphocyte (T cell or B cell), natural killer cell, dendritic cell, or other cell of the immune system or tumor microenvironment.

Abstract: Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000™, FUGENE®, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.

Abstract: Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed, More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.

Abstract: The presently disclosed subject matter provides compositions and methods for using a non-spherical biomimetic artificial cell comprising a three-dimensional microparticle or nanoparticle having an asymmetrical shape and a supported lipid bilayer (SLB). The non-spherical biomimetic artificial cells can be used in cell biomimicry and for active targeting mediated drug delivery.

Abstract: Polymers and nanoparticle formulations for systemic nucleic acid delivery, including mRNA, are disclosed. A bioassay for simultaneously measuring nanoparticle cell uptake and endosomal disruption also is disclosed.

Abstract: A DNA plasmid useful for diagnostic and therapeutic gene therapy is disclosed. Improvements to gene therapy methods known in the art are provided to ensure cancer-targeting, high efficacy, and long durability of expression. The DNA plasmid is combined with compositions of polymeric nanoparticles for non-viral gene therapy to treat cancer, including hepatocellular carcinoma and prostate cancer.

Abstract: The present invention in various aspects and embodiments involves pharmaceutical compositions prepared by contacting a candidate ?- or ?-integrin-binding molecule, or panel thereof, with an integrin heterodimer, and quantifying heterodimer disruption by the candidate molecule. An integrin-binding molecule, or derivative thereof, that disrupts the integrin heterodimer is selected and is formulated into a pharmaceutical composition for administration to a subject, e.g., who has a disease or disorder related to abnormal vascularization.

Abstract: The present invention is a new controlled drug system that can be used for targeting non-invasive neuromodulation enabled by focused ultrasound gated release of one or more small molecule neuromodulatory agents.

Abstract: Biodegradable particles for delivering a nucleic acid encoding gene-editing factors or a nucleic acid associated with a therapeutic protein to a cell, and compositions, methods, systems, and kits for gene editing in vivo or ex vivo or gene therapy for treating retinal eye diseases are disclosed.

Abstract: Cationic polymers having one or more anionic ligand end groups, including a new class of carboxylated branched poly(beta-amino ester)s that can self-assemble into nanoparticles for efficient intracellular delivery of different biomolecules, including a variety of proteins is disclosed.

Abstract: Biodegradable particles for interacting with immune cells to generate an immunosuppressive effect are disclosed. The biodegradable particle comprises a polyester or polyester blend with at least one soluble protein or small molecule encapsulated within the particle and at least two types of protein attached to a surface of the particle or to a coating on the surface thereof, which can be used to induce targeting regulatory T cells (Tregs). The at least two types of protein attached to a surface of the particle or to a coating on the surface thereof include a “Signal 1” protein that binds to an immune cell and a “Signal 2” protein that acts as a co-stimulatory molecule to immune cells. The encapsulated protein can be an interleukin and/or a cytokine. Methods of their use for treating a disease or condition, including an autoimmune disease, are disclosed.

Abstract: The presently disclosed subject matter provides a biomimetic particle platform that can be used to simulate natural cells found throughout the body. The particle comprises a polymeric core of defined shape, size, and mechanical properties and a surface comprising naturally derived cell membranes, such as red blood cells or platelets. Together these features enable a level of biomimicry that can be appropriated for various drug delivery applications and cell engineering applications.

Abstract: The disclosure is directed to a biodegradable particle comprising a polyester or polyester blend, a first protein that binds to an immune cell, and a second protein that promotes proliferation and/or activation of immune cells, and a third soluble protein or small molecule encapsulated within the particle. The second protein is a fusion protein comprising at least a portion of an antibody and at least a portion of a cytokine (i.e., an immunocytokine). The disclosure also is directed to methods for treating a disease or condition in a subject (e.g., an autoimmune disease) comprising administering the aforementioned biodegradable particle to the subject.

Abstract: Synthetic, biodegradable nanoparticles (NPs) encapsulating at least one of a signal 1 protein, a signal 2 protein, and/or a signal 3 protein are disclosed, which, when transfected into one or more a cancer cells, reprogram the one or more cancer cells into “tumor-derived APCs” in vivo to activate T-cells and natural killer (NK) cells for systemic tumor rejection. The NPs can be used for treating cancers, in particular metastatic cancers.

Abstract: Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000™, FUGENE®, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.