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(SD2022-279) Mutant ZRANB2 zinc finger proteins with GGG RNA sequence targeting specificity

Existing RNA-targeting tools for sequence-specific manipulation include anti-sense oligos (ASOs), designer PUF proteins and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas systems. However, there are significant limitations to each of the current tools. ASOs are usually not available for most RNA manipulations other than gene silencing. Designer proteins, such as PUF (Pumilio and FBF homology protein), possess low RNA recognition efficiency and it remains challenging to target RNA sequences >8-nucleotides (nt) in length. The bulky Cas protein (Cas13d: average 930 amino acids) leads to complication for transgene delivery and concerns of its immunogenicity due to its bacterial origin. Mutants of zinc finger(ZnF) proteins in ZRANB2 recognize a single-strand RNA containing a novel GGG motif with micromolar affinity, compared to the original motif GGU. These mutants serve as a foundation for RNA-binding ZnF designer protein engineering for in vivo RNA sequence-specific targeting.ZnFs are generally compact domains (~3kDa each) that have been successfully engineered for DNA recognition as modular arrays. A ZnF-based system has unique advantages, especially in a therapeutic context: (1) Broad application with the possibility to fuse with other effector domains; (2) High efficiency of RNA recognition (3 RNA bases recognized per 30-amino-acid ZnF) with a small size of protein. Only 4 ZnFs (~100 aa) is required for specific targeting in the transcriptome. (3) Humanized components without immunogenic concern.By engineering new sequence specificity of the ZRANB2 ZnF1, researchers from UC San Diego identified 13 mutants that altered their preferred RNA binding motif from GGU to GGG. They are N24R, N24H, N14D/N24R, N14D/N24H, N14R/N24R, N14R/N24H, N14H/N24R, N14H/N24H, N14Q/N24R, N14Q/N24H, N14E/N24R, N14S/N24R, N14E/N24H.

Genetic Polymorphisms Linked to Age-Related Eye Disorders and Drug Response

Researchers at UC Irvine have identified genetic polymorphisms associated with disease progression and responsiveness to treatment with Tetracosapentaenoic acid (24:5 n-3) for age-related eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy and glaucoma. These variations found in the ELOVL2 gene are associated with AMD progression and the varying responses individuals have to AMD treatments, including preventative measures. Additionally, these genetic variations have applications in human identification.

In-situ Production of Anti-inflammatory Lipids for Treating Inflammation

Researchers at the University of California, Davis, have developed a process for isolating anti-inflammatory lipids for treating autoimmune and inflammatory diseases.

Biologic Fish Skin Bandage for Healing Burns and Other Wounds

Researchers at the University of California, Davis have developed a biologic dressing derived from fish skin to enhance wound healing.

Wearable Bioelectronics for Programmable Delivery of Therapy

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Bioelectronic Smart Bandage For Controlling Wound pH through Proton Delivery

Precise control of wound healing depends on physician’s evaluation, experience. Physicians provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. Slow healing of recalcitrant wounds is a known persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. 23% of military blast and burn wounds do not close, affecting a patient’s bone, skin, nerves. 64% of military trauma have abnormal bone growth into soft tissue. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy.

Inverse Design and Fabrication of Controlled Release Structures

Researchers at the University of California, Davis have developed an algorithm for designing and identifying complex structures having custom release profiles for controlled drug delivery.

Molecule for Repairing Leaky Gut And Restoring Energy Metabolism

Researchers at the University of California, Davis have identified an orally administered molecule from microbial origin, capable of repairing damaged gut epithelial barriers and restoring energy metabolism.

Drug Inhibition of NLRP3 Inflammasome Activation

This technology provides a novel insight into the NLRP3 inflammasome's role in the immune response and introduces a repurposed drug that inhibits its activation.

Stabilized Amyloid Oligomers and Applications for Alzheimer’s Research and Treatment

An innovative approach to advancing Alzheimer's disease research, detection, and treatment through the development of synthetic amyloid peptides and oligomers.

Tetracosapentaenoic Acid Treatment for AMD, Diabetic Retinopathy and Glaucoma

An innovative approach using tetracosapentaenoic acid to treat age-related eye disorders by replenishing critical lipids in the retina.

(SD2022-222) Optimized CAG repeat‐targeting CRISPR/cas13d designs

Reseachers from UC San Diego demonstrated a proof of principle for a CAGEX RNA-targeting CRISPR–Cas13d system as a potential allele-sensitive therapeutic approach for HD, a strategy with broad implications for the treatment of other neurodegenerative disorders.

4-N-Derivatized Sialic Acids and Related Sialosides

Researchers at the University of California, Davis have developed advanced compounds targeting neuraminidase activity to combat viral infections and understand cellular mechanisms.

Combination Therapy For CNS Lymphoma

Brief description not available

Novel Tumor-Specific Fas Epitope Targeting Antibodies

Researchers at the University of California, Davis have developed a unique approach to target solid tumors using novel Fas-targeting antibodies designed for improved selectivity and efficacy in immunotherapy.

Antibody-Based Chemically Induced Dimerizers (AbCIDs)

This novel technology enables refined temporal control of protein-protein interactions that can be used to regulate cell therapies, including CAR T-cells and “cell factories”.

Simultaneous 225Ac & 18F Production with Standard Medical Cyclotrons

High flux (e.g., greater than 1012 n/s/cm2) neutrons with energies between 8 and 30 MeV are needed for a number of applications including radioisotope production. However, none of the existing neutron sources available can fulfill these requirements. Neutron flux intensities from typical neutron sources using Deuterium-Tritium (DT) fusion are typically more than 2 orders of magnitude lower in intensity than what is needed for making production practical. Deuterium-Deuterium (DD) fusion sources provide a spectrum which is too low in energy to perform the nuclear reactions needed for isotope production. High-energy proton accelerator-driven spallation sources produce isotopes with significant co-production of unwanted radioisotopes, due to a neutron spectrum which is far higher in energy than required. While accelerator-driven neutron sources using deuteron breakup have been shown to be a viable pathway for producing a range of isotopes including actinium-225 1, a limited number of machines capable of producing ~30 MeV deuteron beams exist commercially. To address this problem, researchers at UC Berkeley have developed systems and methods for producing radionuclides using accelerator-driven fast neutron sources, and more specifically for producing actinium-225, an inherently-safe, fast neutron source based on low energy proton accelerators used throughout the world to support positron emission tomography.

Novel CAR-T Therapy for Glioblastoma

Brief description not available

Use of Ophthalmic Acid for treatment of Parkinson’s disease

Researchers at UC Irvine have identified Opthalmic acid (Ophthalmate, OA) for treatment of Parkinson’s disease (PD), a degenerative neurological disorder that affects 1-2% of people over the age of 60. PD is characterized by progressive motor symptoms such as tremor, rigidity, slowness of movement and difficulty with balance. There is currently no cure for Parkinson’s disease, only treatments to help manage the symptoms. Pharmacological strategies for treating PD depend mainly on replacing lost dopamine due to the degeneration of dopamine neurons in the substantia nigra compacta. Six decades after its initial use, L-3, 4-dihydroxyphenylalalnine (L-DOPA), the dopamine precursor, remains the standard of care for treatment of PD motor symptoms. L-DOPA can readily cross the blood-brain barrier (BBB) and is converted to dopamine by aromatic amino acid decarboxylase (AADC). Initial treatments with L-DOPA can provide great relief from motor symptoms, but over time its therapeutic effects diminish, and dyskinesia (abnormal involuntary movements) can increase in PD patients. Ophthalmic acid acts as a novel neurotransmitter to counteract the motor symptoms in animal models of PD, with a longer duration of action. Ophthalmic acid can be used as a novel drug for treatment of PD and other neurological disorders.

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