A5061801006- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
- CAR-T cell therapy research
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Algal biology and biofuel production
- Advanced biosensing and bioanalysis techniques
- Enzyme Structure and Function
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- DNA and Nucleic Acid Chemistry
- Cancer, Hypoxia, and Metabolism
- Photosynthetic Processes and Mechanisms
- Genomics and Phylogenetic Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Microbial Metabolic Engineering and Bioproduction
- Cancer Genomics and Diagnostics
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Advanced Biosensing Techniques and Applications
- biodegradable polymer synthesis and properties
- Immune Cell Function and Interaction
Synthetic Genomics (United States)
2020-2021
Salk Institute for Biological Studies
2014
Franklin & Marshall College
2007-2012
University of California System
2012
University of California, San Diego
2010
Carnegie Mellon University
2010
Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions demonstrate immunogenicity safety preclinical clinical development. Optimized vaccines generate protective immunity (according WHO defined thresholds) at doses up 1,000,000-fold lower than female...
The experimental study of protein folding is enhanced by the use nonintrusive probes that are sensitive to local conformational changes in structure. Here, we report selection an aminoacyl-tRNA synthetase/tRNA pair for cotranslational, site-specific incorporation two unnatural amino acids can function as fluorescence resonance energy transfer (FRET) donors with Trp probe disruption hydrophobic core upon unfolding. l-4-Cyanophenylalanine (pCNPhe) and 4-ethynylphenylalanine (pENPhe) were...
Despite the importance of protein−polymer bioconjugates, there is no general method for producing homogeneous recombinant protein that contains polymer initiators at defined sites. To address this deficiency, we designed amino acid 4-(2′-bromoisobutyramido)phenylalanine (1) as an initiator in atom-transfer radical polymerization (ATRP) would provide a stable linkage between and growing polymer. We synthesized 1 evolved Methanococcus jannaschii tyrosyl-tRNA synthetase/tRNACUA pair to...
Genetically incorporated unnatural amino acid (UAA) technologies are powerful tools that greatly enhancing our ability to study and engineer biological systems. Using these techniques, researchers can precisely control the position number of novel chemical moieties in a protein, via introducing R group UAAs, genetically encoded protein's primary structure. The substrate recognition properties natural aminoacyl-tRNA synthetase (aaRS) must be modified order incorporate UAAs into proteins....
The use of noncoded amino acids as spectroscopic probes protein folding and function is growing rapidly, in large part because advances the methodology for their incorporation. Recently p-cyanophenylalanine has been employed a fluorescence IR probe, well FRET probe to study folding, protein−membrane interactions, protein−protein interactions amyloid formation. shown be exquisitely sensitive hydrogen bonding involving cyano group, its quantum yield increases dramatically when it bonded....
Many unnatural amino acid synthetases have been evolved to enable the site-specific in vivo incorporation of many useful functionalities into proteins. While these acid-tRNA synthetase-tRNA(CUA) pairs do not incorporate endogenous acids, their substrate specificity has assessed for other acids. Here we demonstrate that can be permissive substrates. The utility further expanded by manipulating synthetase active sites mutagenesis. also shown an l-2-naphthylalanine converted a...
Protein-polymer hybrids (PPHs) represent an important and rapidly expanding class of biomaterials. Typically in these the linkage between protein polymer is covalent. Here we describe a straightforward approach to noncovalent PPH that mediated by DNA. Although noncovalent, DNA-mediated affords highly specific pairing assembly properties To obtain protein-DNA conjugate for PPH, report here first direct copper catalyzed azide-alkyne cycloaddition-based conjugation. This significantly...
Historically poor clinical results of tumor vaccines have been attributed to weakly immunogenic antigen targets, limited specificity, and vaccine platforms that fail induce high-quality polyfunctional T cells, central mediating cellular immunity. We show here the combination selection, construct design, a robust platform based on Synthetically Modified Alpha Replicon RNA Technology (SMARRT), self-replicating RNA, leads control growth in mice. Therapeutic immunization with SMARRT...
Abstract Drug resistance remains the major driving factor behind clinical failure of targeted therapeutics. Current oncology precision medicine approaches rely on targeting known acquired mutations, such as EGFR T790M or ALK/ROS mutations in NSCLC with 2nd and 3rd generation molecules designed to overcome prevent resistance. These next therapeutic have increasingly long complex drug development timelines burdensome toxicities from off target effects (e.g. wild-type receptor targeting)...
e14543 Background: Growth factor and p16-CDK-RB-E2F pathway components are mutated in almost all cancers, resulting oncogenic E2F transcriptional activity that drives uncontrolled proliferation. Chemotherapies indiscriminately kill proliferating cells, limiting toxicities. CDK inhibitors more targeted but cytostatic as opposed to tumoricidal. was discovered a transcribes adenovirus (Ad) E2 cellular genes drive viral replication. Ad E1A binds RB, which activates E2F. On this basis, viruses...
Abstract Protein drug replacement using nucleic acid technologies has been a sought-after solution for in situ production of proteins with poor half-lives and challenging manufacturability. Linear mRNA approaches have failed clinically this technological use case due to low levels protein expression durability. Self-replicating RNA (srRNA) is new technology biotherapeutics combining the advantages fully synthetic products higher peak active persisting out 49 days. RBI-2000 novel srRNA...
<h3>Background</h3> Melanoma remains a daunting clinical challenge. Immunotherapy the mainstay in treatment of metastatic disease. Yet, nearly 50% patients fail to respond immunotherapy, due multiple potential mechanisms ICI resistance but acquired and innate. One key mechanism is suppressive nature tumor microenvironment (TME), driven large part highly inflamed melanoma metastases. Though beneficial efficacy, prolonged inflammation co-opted by as pro-growth factor leads localized...
Genetically incorporated unnatural amino acid (UAA) technologies are powerful tools that greatly enhancing our ability to study and engineer biological systems. To incorporate UAAs into protein, the substrate recognition properties of an aminoacyl‐tRNA synthetase (RS) must be modified. Protocols do so technically simple but require time optimization, which has significantly limited accessibly this important technology. At present, engineered RSs evaluated on their efficiency fidelity. We...