A5012304889- Origins and Evolution of Life
- DNA and Nucleic Acid Chemistry
- Supramolecular Self-Assembly in Materials
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Photoreceptor and optogenetics research
- Amino Acid Enzymes and Metabolism
- Supramolecular Chemistry and Complexes
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- Chemical Analysis and Environmental Impact
- Metabolism and Genetic Disorders
- Organophosphorus compounds synthesis
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- Crystallography and molecular interactions
- Molecular Junctions and Nanostructures
- DNA and Biological Computing
- Advanced Materials and Mechanics
- Glycogen Storage Diseases and Myoclonus
- Advanced Sensor and Energy Harvesting Materials
- Modular Robots and Swarm Intelligence
- Photochromic and Fluorescence Chemistry
Harvard University
2017-2024
Akebia Therapeutics (United States)
2021-2023
Beam Therapeutics (United States)
2022
Georgia Institute of Technology
2012-2021
AID Atlanta
2014-2018
Harvard University Press
2017
Tulane University
2015
The delivery of genetic material to cells offers the potential treat many diseases. Cationic polymers, specifically poly(ethylene imine) (PEI), are promising gene vectors due their inherent ability condense and successfully affect its transfection. However, PEI other cationic polymers also exhibit high cytotoxicity. To systematically study effect polymer architecture on efficiency cell cytotoxicity, a set cyclic PEIs were prepared for first time compared linear exact same molecular weight....
Molecular self-assembly is widely appreciated to result from a delicate balance between several noncovalent interactions and solvation effects. However, current design approaches for achieving in water with small, synthetic molecules do not consider all aspects of the hydrophobic effect, particular requirement surface areas greater than 1 nm2 an appreciable free energy hydration. With concept minimum area mind, we designed system that achieves highly cooperative water. Two weakly interacting...
Abstract The RNA World hypothesis presupposes that abiotic reactions originally produced nucleotides, the monomers of and universal constituents metabolism. However, compatible prebiotic for synthesis complementary (that is, base pairing) nucleotides mechanisms their mutual selection within a complex chemical environment have not been reported. Here we show two plausible heterocycles, melamine barbituric acid, form glycosidic linkages with ribose ribose-5-phosphate in water to produce...
Abstract The poor reactivity of insoluble phosphates, such as apatite‐group minerals, has been a long‐appreciated obstacle for proposed models prebiotic organophosphate formation. This presents significant challenge to the nascent development an RNA world and other origins life on Earth. Herein, we demonstrate that scenario based formation urea/ammonium formate/water (UAFW) eutectic solution leads increase in phosphorylation when compared urea alone phosphate sources varying solubility. In...
Although information is ubiquitous, and its technology arguably among the highest that humankind has produced, very ubiquity posed new types of problems. Three involve storage (rather than computation) include usage energy, robustness stored over long times, ability to resist corruption through tampering. The difficulty in solving these problems using present methods stimulated interest possibilities available fundamentally different strategies, including molecules. Here we show mixtures...
The RNA World hypothesis is central to many current theories regarding the origin and early evolution of life. However, formation by plausible prebiotic reactions remains problematic. Formidable challenges include glycosidic bond between ribose canonical nucleobases, as well inability nucleosides mutually select their pairing partners from a complex mixture other molecules prior polymerization. Here we report one-pot model reaction pyrimidine nucleobase (2,4,6-triaminopyrimidine, TAP)...
Aqueous solutions of the achiral, monomeric, nucleobase mimics (2,4,6-triaminopyrimidine, TAP, and a cyanuric acid derivative, CyCo6) spontaneously assemble into macroscopic homochiral domains supramolecular polymers. These assemblies exhibit high degree chiral amplification. Addition small quantity one handedness derivative CyCo6 generates exclusively structures. This system exhibits highest reported amplification for dynamic helical polymers or helices. Significantly, comprised hexameric...
This work describes the autocatalytic copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction between tripropargylamine and 2-azidoethanol in presence of Cu(II) salts. The product this reaction, tris-(hydroxyethyltriazolylmethyl)amine (N(C3N3)3), accelerates (and thus its own production) by two mechanisms: (i) coordinating promoting reduction to Cu(I) (ii) enhancing catalytic reactivity step. Because cooperation these processes, a rate enhancement >400× is observed over course reaction....
How simple chemical reactions self-assembled into complex, robust networks at the origin of life is unknown. This general problem—self-assembly dissipative molecular networks—is also important in understanding growth complexity from simplicity and biomolecular systems. Here, we describe how heterogeneity composition a small network oscillatory organic can sustain (rather than stop) these oscillations, when homogeneity their does not. Specifically, multiple reactants an amide-forming...
Streptococcus pyogenes (Spy) Cas9 has potential as a component of gene therapeutics for incurable diseases. One its limitations is large size, which impedes formulation and delivery in therapeutic applications. Smaller Cas9s are an alternative, but lack robust activity or specificity frequently recognize longer PAMs. Here, we investigated four uncharacterized, smaller found three employing "GG" dinucleotide PAM similar to SpyCas9. Protein engineering generated synthetic RNA-guided nucleases...
Alpha-1 antitrypsin deficiency (AATD) is a rare autosomal codominant disease caused by mutations within the SERPINA1 gene. The most prevalent variant in patients PiZ SERPINA1, containing single G > A transition mutation. alpha-1 (AAT) prone to misfolding, leading accumulation of toxic aggregates hepatocytes. In addition, abnormally low level AAT secreted into circulation provides insufficient inhibition neutrophil elastase lungs, eventually causing emphysema. Cytosine and adenine base...
Abstract Uncovering the origin of RNA is essential for understanding origins life. The persistent inability chemists to identify a plausible prebiotic route polymers, along with seemingly optimal structure its functions in extant life, argue favor hypothesis that product chemical or biological evolution. To understand RNA, we must consider which molecules could have originally acted place RNA’s substructures (i.e., nucleobases (the recognition units), ribose (a trifunctional connector), and...
The rapidly increasing use of digital technologies requires the rethinking methods to store data. This work shows that data can be stored in mixtures fluorescent dye molecules, which are deposited on a surface by inkjet printing, where an amide bond tethers molecules surface. A microscope equipped with multichannel fluorescence detector distinguishes individual dyes mixture. presence or absence these mixture encodes binary information (i.e., "0" "1"). instead sequence-defined macromolecules,...
The hypothesis that RNA and DNA are products of chemical biological evolution has motivated our search for alternative nucleic acids may have come earlier in the emergence life-polymers possess a proclivity covalent non-covalent self-assembly not exhibited by RNA. Our investigations revealed small set candidate ancestral nucleobases self-assemble into hexameric rosettes stack water to form long, twisted, rigid supramolecular polymers. These structures exhibit properties provide robust...
p<italic>K</italic><sub>a</sub>-matched monomers self-assemble into supramolecular polymers at pH 7, producing hydrogels with high sensitivity.
Phosphorylation reactions of glycerol were studied using different inorganic phosphates such as sodium phosphate, trimetaphosphate (a condensed phosphate), and struvite. The carried out in two non-aqueous solvents: formamide a eutectic solvent consisting choline-chloride ratio 1:2.5. reacted the with phosphate to yield its phosphorylated derivatives presence silicates quartz sand kaolinite clay. by heating source at 85 °C for one week analyzed 31P-nuclear magnetic resonance (NMR)...
Abstract This paper describes the fabrication of elastomeric three‐dimensional (3D) structures starting from two‐dimensional (2D) sheets using a combination direct‐ink printing and relaxation strain. These are fabricated in two‐step process: first, inks deposited as 2D on stretched sheet, second, after curing inks, strain sheet causes it to deform into 3D shape. To predict bending objects with this technique, simple mechanical model is developed. The strategy initially materials fabricate...
The free nucleobases and mononucleotides of RNA do not form Watson–Crick base pairs in water, a fact that presents several challenges for the prebiotic synthesis RNA.
To test the hypothesis that an abiotic Earth and its inert atmosphere could form chemically reactive carbon- nitrogen-containing compounds, we designed a plasma electrochemical setup to mimic lightning-induced electrochemistry under steady-state conditions of early Earth. Air-gap reactions at air-water-ground interfaces lead remarkable yields, with up 40 moles carbon dioxide being reduced into monoxide formic acid, 3 gaseous nitrogen fixed nitrate, nitrite, ammonium ions, per mole...
Abstract The poor reactivity of insoluble phosphates, such as apatite‐group minerals, has been a long‐appreciated obstacle for proposed models prebiotic organophosphate formation. This presents significant challenge to the nascent development an RNA world and other origins life on Earth. Herein, we demonstrate that scenario based formation urea/ammonium formate/water (UAFW) eutectic solution leads increase in phosphorylation when compared urea alone phosphate sources varying solubility. In...
The simple and reversible control of the degree polymerization, thereby bulk material properties, a supramolecular polymer is reported. Noncovalent capping agents (chain stoppers) modulate length polymers by stacking on surfaces polymer's ends. Methylene blue (MB) positively charged, planar polycyclic dye that acts as chain stopper. It can be reversibly switched between its colored, planar, cationic state colorless, nonplanar, neutral (leucomethylene blue, LMB) reduction with ascorbic acid...
We propose that chitosan can be used as an efficient pH-responsive protective layer for pH sensitive soft materials.
Nonenzymatic DNA ligation chemistries containing a reversible step allow thermodynamic control of product formation, but they are not necessarily compatible with polymerase enzymes. We report system that uses commercially available reagents, includes step, and results in linkage can function as template for PCR amplification accurate sequence transfer.