A5060263375- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- RNA regulation and disease
- Virus-based gene therapy research
- RNA Research and Splicing
- Evolution and Genetic Dynamics
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Bacterial Infections and Vaccines
- Ion channel regulation and function
- Protein Degradation and Inhibitors
- Pain Mechanisms and Treatments
- Evolutionary Game Theory and Cooperation
- Pneumonia and Respiratory Infections
- Pluripotent Stem Cells Research
- Toxin Mechanisms and Immunotoxins
- Advancements in Transdermal Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neuropharmacology Research
- Botulinum Toxin and Related Neurological Disorders
- Cancer Research and Treatments
- Genetics, Aging, and Longevity in Model Organisms
University of California, San Diego
2018-2024
La Jolla Bioengineering Institute
2022
National Institute for Biological Standards and Control
2017-2020
Agency for Science, Technology and Research
2020
Institute of Molecular and Cell Biology
2020
Arizona State University
2018
Current treatments for chronic pain rely largely on opioids despite their substantial side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing. In particular, a hereditary loss-of-function mutation Na
Evolutionary innovations are often achieved by repurposing existing genes to perform new functions; however, the mechanisms enabling transition from old remain controversial. We identified mutations in bacteriophage λ's host-recognition gene J that confer enhanced adsorption native receptor, LamB, and ability access a OmpF. The destabilize λ particles cause conformational bistability of J, which yields progeny multiple phenotypic forms, each proficient at different receptors. This work...
Adenosine deaminases acting on RNA (ADARs) can be repurposed to enable programmable editing, however their exogenous delivery leads transcriptome-wide off-targeting, and additionally, enzymatic activity certain motifs, especially those flanked by a 5’ guanosine is very low thus limiting utility as transcriptome engineering toolset. Towards addressing these issues, we first performed novel deep mutational scan of the ADAR2 deaminase domain, directly measuring impact every amino acid...
ABSTRACT A major hurdle in protein-based therapeutics is the interaction with adaptive immune system, which can lead to neutralization by circulating antibodies and clearance of treated cells cytotoxic T-lymphocytes. One method circumventing these issues use human or humanized proteins avoid response self-recognition. However, this approach limits potential protein those origin, excluding many exciting effectors delivery vehicles such as CRISPR-Cas9 adeno-associated viruses (AAVs). To...
ABSTRACT Adeno-associated viruses (AAVs) are common gene therapy vectors, however, their effectiveness is hindered by poor target tissue transduction and off-target delivery. Hypothesizing that naturally occurring receptor-ligand interactions could be repurposed to engineer tropism, we fragmented all annotated protein ligands known bind human receptors into tiling 20-mer peptides displayed these onto the surface loops of AAV5 AAV9 capsids at two sites. The resulting four capsid libraries,...
ABSTRACT Adenosine deaminases acting on RNA (ADARs) can be repurposed to enable programmable editing, however their exogenous delivery leads transcriptome-wide off-targeting, and additionally, enzymatic activity certain motifs, especially those flanked by a 5’ guanosine is very low thus limiting utility as transcriptome engineering toolset. To address this, we explored comprehensive ADAR2 protein via three approaches: First, performed novel deep mutational scan of the deaminase domain that...
Abstract Sexual recombination only occurs in eukaryotes; however, many bacteria can actively recombine with environmental DNA. This behavior, referred to as transformation, has been described species from diverse taxonomic backgrounds. Transformation is hypothesized carry some selective advantages similar those postulated for meiotic sex eukaryotes. However, the accumulation of loss-of-function alleles at transformation loci and an increased mutational load recombining DNA dead cells create...
ABSTRACT RNAs are a powerful therapeutic class. However their inherent transience impacts activity both as an interacting moiety well template. Circularization of RNA has been demonstrated means to improve persistence, however simple and scalable approaches achieve this lacking. Utilizing autocatalytic circularization, here we engineer i n situ c ircularized (icRNAs). This approach enables icRNA delivery linear that is circularized upon into the cell, thus making them compatible with routine...
Aim To evaluate the immunogenicity of a recombinant protein D from Haemophilus Influenzae (Hi) and functional activities induced antibodies in mouse model. Methods Female Balb/c mice were immunised subcutaneously with presence or absence adjuvants serum immunoglobulin G (IgG) response to was assessed by ELISA. The activity immune sera evaluated vitro using bactericidal assay against typeable Hi serotype b (Hib) non-typeable (NTHi) clinical isolates vivo an infant rat bacteraemia model Hib...