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Computationally predicts potential ideal interaction points for the molecular chaperone heat shock protein-90 (Hsp90). Background:
Molecular chaperones assist in the folding of unfolded and misfolded polypeptides by stabilization of folding intermediates and prevention of protein misfolding and aggregation. Molecular chaperones are present in all organisms and are essential for cell survival. The chaperone heat shock protein-90 (Hsp90) controls the folding of client proteins important for tumorigenesis. Hsp90 facilitates the maturation of substrates (or clients) that are involved in many different cellular pathways. Hsp90 clients include, among others, kinases, transcription factors, steroid hormone receptors and E3 ubiquitin ligases. The development of Hsp90 ATP-competitive inhibitors has been limited partly because it results in the simultaneous blockage of all clients, ultimately causing antiapoptotic heat shock response.Technology Overview:  
This technology computationally predicts the most unstable regions on the native structures of clients c-Abl, c-Src, Cdk4, B-Raf and Glucocorticoid Receptor, as potential ideal interaction points with the Hsp90-system. This enables researchers to synthesize peptide mimics spanning these regions and confirm their interaction with partners of the Hsp90 complex (Hsp90, Cdc37 and Aha1) by Nuclear Magnetic Resonance (NMR). Designed non-naturally occurring peptides selectively disrupt the association of their respective clients with the Hsp90 machinery, leaving unrelated clients unperturbed and causing apoptosis in cancer cells. Overall, selective targeting of Hsp90 protein-protein interactions is achieved without causing indiscriminate degradation of all clients, setting the stage for the development of therapeutics based on specific chaperone:client perturbation.
 https://suny.technologypublisher.com/files/sites/adobestock_4870932151.jpegAdvantages:  
•    Enables the development of therapeutics based on Hsp90.
•    Avoids antiapoptotic heat shock response.  Applications:  
The primary application for this technology is the development of therapeutics based on Hsp90.  Intellectual Property Summary:
PCT Nationalized, including US2021/0214734 and EP4090679Stage of Development:
TRL 3 - Experimental proof of concept Licensing Status:
This technology is available for licensing.Licensing Potential:
This technology would be of interest to anyone involved in the development of therapeutics based on Hsp90, including:
•    Pharmaceutical manufactures.
•    Hospitals.
•    Medical laboratories.
•    Universities.

­A killed ZIKA vaccine that prevents infection and is safe for pregnant women. Background:
Zika virus (ZIKV) is a Flavivirus transmitted by mosquitoes. First discovered in 1947, it remained a minor infectious entity until 2007, when the first large outbreak was reported in Micronesia. Subsequent severe outbreaks in French Polynesia (2013-14) and in Brazil (2015) put ZIKV on the map. Those outbreaks showed that Zika Virus is not only transmitted by mosquitos, but also by sexual contact and in utero, from Mom to fetus. While most people infected with ZIKV have few to no symptoms; the outbreak in Brazil was associated with increased microencephaly, with other severe congenital malformations, and with neurological complications.By 2016, 39 countries and territories in the Americas had confirmed local, vector-borne transmission of ZIKV as well as superinfection from one person to another. That, coupled with the severity of symptoms, triggered a campaign to create a robust ZIKV vaccine.Technology Overview:  
In a collaborative effort, scientists in the Army and at SUNY have created and tested a killed ZIKA vaccine. It has undergone Phase 1 and 2 testing in pregnant mouse and pregnant marmoset models. It has also been tested in humans.
Further Details:

1. Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2020 Sep;20(9):1061-1070. doi: 10.1016/S1473-3099(20)30085-2. Epub 2020 May 6. PMID: 32618279; PMCID: PMC7472641. (https://pubmed.ncbi.nlm.nih.gov/32618279/) 
2. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials. Lancet. 2018 Feb 10;391(10120):563-571. doi: 10.1016/S0140-6736(17)33106-9. Epub 2017 Dec 5. Erratum in: Lancet. 2020 Jun 20;395(10241):1906. PMID: 29217375; PMCID:PMC5884730. (https://pubmed.ncbi.nlm.nih.gov/29217375/) 
3. Sci Transl Med. 2017 Dec 13;9(420):eaao4163. doi: 10.1126/scitranslmed.aao4163. Erratum in: Sci Transl Med. 2018 Jul 18;10(450):PMID: 29237759; PMCID: PMC5747972. (https://pubmed.ncbi.nlm.nih.gov/29237759/)

https://suny.technologypublisher.com/files/sites/adobestock_1194681161.jpegAdvantages:  
•    Broad application  Applications:  
•    Prevention of ZIKV infection with a vaccine that is safe even for pregnant women.
 
Intellectual Property Summary: Zika virus vaccine and Methods of Production is protected by patent 11,033,615 which issued on June 15, 2021 https://patents.google.com/patent/US11033615B2/
Stage of Development:
TRL 4 – Technology validated in lab
Licensing Status:
This technology is available for licensing.
 

Targeted gene silencing technology promotes corneal wound healing. Background: Ocular scarring after surgery, trauma, or infection leads to vision loss and blindness. Blindness due to corneal scarring can currently only be resolved by transplantation, necessitating new approaches in regenerative wound healing in the eye.Technology Overview:  A self-deliverable siRNA has been developed by Upstate Medical University researchers to specifically target a gene that modulates scarring in order to promote corneal wound healing. The approach has been validated ex vivo and in vivo, with treatment after corneal wounding resulting in faster wound closure, limited scarring, suppression of fibrotic markers, and restoration of corneal thickness. https://suny.technologypublisher.com/files/sites/110-2089.jpghttps://www.pexels.com/photo/human-eye-2609925/Advantages:  

• Targeted siRNA therapy circumvents the need for immunologically compatible corneal donors.
• In vivo studies demonstrate this therapy promotes 41.5% reduction in scarring

  Applications:  

• Effective treatment for corneal scarring resulting from mechanical injuries, burns, infections or surgery.
• Model useful to study pathogenesis of fibrotic healing.

Licensing Status: Available for licensing or collaboration.

Novel nanocarrier for systemic and intracellular delivery of biological therapeutics. Background: The stability and PK profile are of general concern for in vivo applications of many peptide/protein therapeutics. Poor stability of protein drugs can trigger immunogenicity. Furthermore, peptide and protein therapeutics mostly target extracellular receptors/signaling pathways and are impermeable to plasma membranes for interacting with the intracellular targets. Conventional nanoparticles designed for protein encapsulation and controlled release are generally associated with protein denaturation due to the extra manipulation together with unwanted chemical residues remaining in the formulation. The suite of technologies described herein seeks to overcome these challenges through molecular innovation in nanocarrier development for in situ protein encapsulation and intracellular protein delivery.Technology Overview:  This innovative technology portfolio from Upstate Medical University provides multiple chemical formulations of telodendrimer nanocarriers made from biocompatible polyethylene glycol, amino acids, and natural hydrophobic compounds. The resulting nanocarriers binds to protein therapeutics via well-defined multivalent charge and hydrophobic interactions. Telodendrimer refers to a linear-dendritic copolymer, containing a hydrophilic segment (i.e., PEG or zwitterionic moiety) and one dendritic domain with the peripheral groups covalently capped with well-defined chemical moieties. Telodendrimers can be customized and optimized via computational and combinatorial approaches based on the charge and surface pocket of the cargo protein. These telodendrimers have well-defined flexible, multivalent, and hybrid branched functional domains for effective in situ protein encapsulation in solution driven by affinity.

Several types of proteins and peptides can be encapsulated in telodendrimers including, but are not limited to, cytokines, diphtheria toxin, cytochrome c, insulin, GLP-1 peptide, liragrutide, antibodies, growth factors, i.e., , VEGF, etc. This highly customizable nanotechnology platform permits the synthesis of nanocarriers to coat a variety of proteins in situ by simple addition of two solutions together forming both protein-friendly and patient-friendly formulation for in vivo applications. This telodendrimer coating significantly improves the PK profile in blood circulation with the capability to deliver cargo proteins intracellularly. https://suny.technologypublisher.com/files/sites/110-2024.jpgAdvantages:  
 •   Well-defined structures facilitating easy quality control and better reproducibility for regulation compliance;
•    In situ protein encapsulation that avoids protein denaturation and unwanted chemical residues;
•    Improved in vitro and in vivo protein/peptide stability and PK profiles;
•    Intracellular delivery capability;
•    High loading capacity: 20%-100% of the nanocarriers by weight;
•    Maintenance of bioactivity of protein/peptide therapeutics for both topical and systemic delivery. 
Applications:  
•    Delivery of Insulin, GLP-1, Liraglutide for diabetes treatment.
•    Intracellular delivery of diphtheria toxin, cytochrome C or antibodies for cancer treatment.
•    Local delivery and control release of growth factors, e.g. VEGF, FGF for tissue regeneration.
•    Improved systemic delivery of antibody therapeutics or enzymes or peptide/protein hormones with enhanced in vitro and in vivo stability, reduced immunogenicity and prolonged pharmacokinetic profiles.
•    Delivery of cytokines for immune modulation therapy.  Intellectual Property Summary:

• Compositions and devices for removal of endotoxins and cytokines from fluids
• Functional, Segregated, Charged Telodendrimers and Nanocarriers and Methods of Making and Using the Same - EP3347053A1 and US20190292328A1
• Telodendrimers with Riboflavin Moieties and Nanocarriers and Methods of Making and Using the Same -WO2018136778A1 and US20190328742A1
• Zwitterionic dendritic amphiphiles, zwitterionic dendrimers, zwitterionic telodendrimers, nanocarriers comprising same, and methods of making and using same - WO2018160759A1 and US20200009069A1

Stage of Development:

• In vivo and ex vivo studies in mouse models for cancer, diabetes, psoriasis, and sepsis have been completed
• https://en.wikipedia.org/wiki/Technology_readiness_level

Licensing Status:  Patented  Licensing Potential:  Seeking an industry partner to license the technology or partner to further technical development.  Additional Information:  

1. Shi C, Wang X, Wang L, Meng Q, Guo D, Chen L, Dai M, Wang G, Cooney R, Luo J.* A nanotrap improves survival in severe sepsis by attenuating hyperinflammation. Nat Commun. 2020 Jul 7;11(1):3384. https://www.nature.com/articles/s41467-020-17153-0
2. Guo, D., Shi, C., Wang, L., Ji, X., Zhang, S. & Luo, J.* Rationally Designed Micellar Nanocarriers for the Delivery of Hydrophilic Methotrexate in Psoriasis Treatment. ACS Applied Bio Materials 2020, 3, 8, 4832–4846 https://pubs.acs.org/doi/10.1021/acsabm.0c00342
3. Wang L, Shi C, Wang X, Guo D, Duncan TM, Luo J.* Zwitterionic Janus Dendrimer with distinct functional disparity for enhanced protein delivery. Biomaterials. 2019 Sep;215:119233. https://www.sciencedirect.com/science/article/pii/S0142961219303321
4. Wang X, Shi C, Zhang L, Bodman A, Guo D, Wang L, Hall WA, Wilkens S, Luo J.* Affinity-controlled protein encapsulation into sub- 30 nm telodendrimer nanocarriers by multivalent and synergistic interactions. Biomaterials. 2016 Sep;101:258-71. https://www.sciencedirect.com/science/article/pii/S0142961216302605
5. Wang X, Bodman A, Shi C, Guo D, Wang L, Luo J.*, Hall WA. Tunable Lipidoid-Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment. Small. 2016 Aug;12(31):4185-92. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201601234