A5101740993- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Silicone and Siloxane Chemistry
- Organoboron and organosilicon chemistry
- RNA regulation and disease
- Synthesis and characterization of novel inorganic/organometallic compounds
- Advanced Biosensing Techniques and Applications
- Surface Modification and Superhydrophobicity
- Chromosomal and Genetic Variations
- Catalytic Cross-Coupling Reactions
- Hearing, Cochlea, Tinnitus, Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Polymer Surface Interaction Studies
- Animal Genetics and Reproduction
- SARS-CoV-2 and COVID-19 Research
- Cellular transport and secretion
- Pancreatic function and diabetes
- Immune cells in cancer
- Lipid Membrane Structure and Behavior
- Kawasaki Disease and Coronary Complications
- Histone Deacetylase Inhibitors Research
Broad Institute
2023
Harvard University
2012-2022
Harvard University Press
2022
University of Twente
2021
Howard Hughes Medical Institute
2009-2019
Creighton University
2014
Western University
2011
McMaster University
2007-2010
BACKGROUND. Weeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in (MIS-C). Gastrointestinal (GI) symptoms are common patients with MIS-C, and severe hyperinflammatory response ensues potential for cardiac complications. The cause of MIS-C has not been identified to date.
Nucleic acid reagents, including small interfering RNA (siRNA) and plasmid DNA, are important tools for the study of mammalian cells promising starting points development new therapeutic agents. Realizing their full potential, however, requires nucleic delivery reagents that simple to prepare, effective across many cell lines, nontoxic. We recently described extensive surface mutagenesis proteins in a manner dramatically increases net charge. Here, we report superpositively charged green...
The inefficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential many proteins. We and others have previously shown that superpositively charged are efficiently endocytosed can bring associated nucleic acids cells. vast majority cargo delivered in this manner, however, endosomes does not reach cytosol. In study we designed implemented screen discover peptides enhance endosomal escape fused GFP (+36 GFP). From reported disrupt microbial...
Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss humans. Using a mouse model Atp2b2
Few routes to well-defined 3D silicone structures exist because of their susceptibility depolymerization/metathesis in the presence acids or bases. The Lewis acid B(C6F5)3 can be employed condense hydrosilanes with alkoxysilanes, producing siloxanes and alkanes (R3SiH+R'OSiR' '3 --> R3SiOSiR' + R'H). We demonstrate that balancing steric demands at both hydrosilane careful control reaction conditions, permits clean condensation reactions occur absence competing metathesis processes. resulting...
The Piers-Rubinsztajn reaction, involving B(C(6)F(5))(3)-catalyzed siloxane formation from hydrosilanes + alkoxysilanes, is tolerant of a wide variety functional groups, and provides generic strategy for the preparation structurally complex silicones.
We describe the development of 'recCas9', an RNA-programmed small serine recombinase that functions in mammalian cells. fused a catalytically inactive dCas9 to catalytic domain Gin using optimized fusion architecture. The resulting recCas9 system recombines DNA sites containing minimal core site flanked by guide RNA-specified sequences. show these recombinases can operate on cells identical genomic loci naturally found human genome manner is dependent RNA sequencing reveals catalyzes...
Abstract The development of site-specific recombinases (SSRs) as genome editing agents is limited by the difficulty altering their native DNA specificities. Here we describe Rec-seq, a method for revealing specificity determinants and potential off-target substrates SSRs in comprehensive unbiased manner. We applied Rec-seq to characterize several natural evolved including Cre, variants other SSR family members. profiling these enzymes mutants thereof revealed previously uncharacterized...
Multiplex genome editing is the simultaneous introduction of multiple distinct modifications to a given genome. Though in its infancy, maturation this field will facilitate powerful new biomedical research approaches and enable host far-reaching biological engineering applications, including therapeutic modalities industrial as well "genome writing" de-extinction efforts. In Perspective, we focus on multiplex large eukaryotic genomes. We describe current state multiplexed editing, limits our...
Coronavirus disease 2019 (COVID-19) manifests with high clinical variability and warrants sensitive specific assays to analyze immune responses in infected vaccinated individuals. Using Single Molecule Arrays (Simoa), we developed an assay assess antibody neutralization sensitivity multiplexing capabilities based on antibody-mediated blockage of the ACE2-spike interaction. The does not require live viruses or cells can be performed a biosafety level 2 laboratory within two hours. We used...
Delivery into mammalian cells remains a significant challenge for many applications of proteins as research tools and therapeutics. We recently reported that the fusion cargo to supernegatively charged (-30)GFP enhances encapsulation by cationic lipids delivery cells. To discover polyanionic with optimal properties, we evaluate negatively natural human their ability deliver cultured primary fibroblasts. Here ProTα, small, widely expressed, intrinsically disordered protein, enables up...
While silicone elastomers generally have excellent biomaterials properties, their hydrophobicity can elicit undesired local biological responses through adsorption and denaturation of proteins. Surface-bound poly(ethylene glycol) (PEG) ameliorate the situation by preventing contact between external biology elastomer. It is further possible to manipulate biocompatibility surface linking peptides, proteins or other entities PEG. Previous synthetic approaches PEG-protected surfaces are...
The use of a hyperthermal hydrogen induced cross-linking process to prepare laminates comprising polypropylene, poly(isobutylene-co-isoprene), and poly(vinyl acetate) is described. In this new, milder alternative conventional plasma techniques, neutral molecular projectiles were used create carbon radicals on impacted surfaces by collision-induced dissociation C-H bonds, was cross-link polymers polypropylene surface. It demonstrated that multiple layers cross-linked materials could be added,...