The present application provides nerve growth factor (NGF) variants with improved in vivo stability, methods for producing and purifying NGF variants, as well as potential therapeutic applications.
Delivery Of Macromolecules Into The Central Nervous System Via The Bloodstream
CNS metastases are a major cause of cancer deaths with few therapeutic options for treatment. Monoclonal anti-body-based therapy is one of the most successful therapeutic strategies for cancer; however, its efficacy is limited against CNS metastases due to insufficient CNS delivery. Here, we show significantly improved antibody delivery to the CNS using novel timed-release nanocapsules that encapsulate individual antibodies within a crosslinked phosphorylcholine polymer and gradually release cargo through hydrolysable crosslinkers. A single course of rituximab (RTX) nanocapsule treatment elevates RTX levels in the CNS by nearly 10-fold compared to native RTX. We improved control of CNS metastases in a murine xenograft model of non-Hodgkin lymphoma; moreover, using a xenograft humanized BLT mouse model, lymphomas were eliminated with a single course of RTX nanocapsule treatment. This approach is useful for treatment of cancers with CNS metastases and is generalizable for delivery of any antibody to the CNS.
Novel Rnai Molecule Delivery Platform Based On Single-Sirna And Shrna Nanocapsules
- Oakland CA, US Irvin S.Y. CHEN - Palos Veerdes Estate CA, US Ming YAN - Encino CA, US Min LIANG - Encino CA, US Masakazu KAMATA - Los Angeles CA, US Jing WEN - Culver City CA, US
Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.
Growth-Factor Nanocapsules With Tunable Release Capability For Bone Regeneration
- Oakland CA, US - Los Angeles CA, US - Tianjin, CN Juanjuan Du - San Diego CA, US Jing Wen - Culver City CA, US Yang Liu - Los Angeles CA, US Xubo Yuan - Tianjin, CN
Assignee:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA - Oakland CA THE UNIVERSITY OF SOUTHERN CALIFORNIA - Los Angeles CA TIANJIN UNIVERSITY - Tianjin CA
International Classification:
A61K 9/51 A61K 38/18 B82Y 5/00 A61P 19/00
Abstract:
Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited in by short in vivo half-lives and a narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. A nanoscale controlled release system (degradable protein nanocapsule) is provided via in-situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes are achieved with the growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 (BMP-2) nanocapsules.
Provided herein are novel methods of treating cerebral ischemia, comprising administering a polymer nanocapsule or a composition thereof. Said nanocapsules comprise a polymer shell and an RNAi (e.g., miRNA) molecule, wherein the polymer shell comprises a) at least one positively charged monomer, b) at least one degradable cross-linker, and c) at least one neutral monomer; and the RNAi molecule provides therapeutic benefits to a subject suffering from cerebral ischemia. Also disclosed herein are compositions of said polymer nanocapsules.
Protein Nanocapsules With Detachable Zwitterionic Coating For Protein Delivery
- Oakland CA, US Jie LI - Los Angeles CA, US Yang LIU - Los Angeles CA, US Jie REN - Los Angeles CA, US Jing WEN - Culver City CA, US
International Classification:
A61K 9/51 A61K 38/38
Abstract:
The invention relates to protein nanocapsules that exhibit material properties that change in different in vivo environments. A zwitterion moiety on the surface of the nanocapsule can protect the protein from opsonization in a first environment, yet uncouples from the protein nanocapsule in a second environment (e.g. at a pH of less than 6.5). In embodiments of the invention, the uncoupled protein nanocarrier is then internalized by mammalian cells (e.g. tumor cells).
Enzyme Responsive Nanocapsules For Protein Delivery
- Oakland CA, US Tatiana Segura - Los Angeles CA, US Suwei Zhu - Los Angeles CA, US Jing Wen - Culver City CA, US
Assignee:
The Regents of the University of California - Oakland CA
International Classification:
A61K 9/51 A61K 47/65 A61K 9/19 A61K 38/18
Abstract:
The invention provides methods of making and using compositions comprising a polymer shell designed to deliver polypeptides to selected environments. In embodiments of the invention, different environmental conditions are harnessed to allow the selective degradation of the polymer shell and the consequential release of one or polypeptides encapsulated therein. In illustrative embodiments, polymer components of the shell are interconnected by peptide-containing crosslinker to moieties, linkages which maintain the integrity of the polymer shell under certain enviromental conditions, but can also be cleaved when combined with a selected protease.
Compositions And Methods For Recombinant Nerve Growth Factor
The present application provides nerve growth factor (NGF) variants with improved in vivo stability, methods for producing and purifying NGF variants, as well as potential therapeutic applications.
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