- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
- Gold and Silver Nanoparticles Synthesis and Applications
- SARS-CoV-2 detection and testing
- Polymer Surface Interaction Studies
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- X-ray Diffraction in Crystallography
- SARS-CoV-2 and COVID-19 Research
- Nanofabrication and Lithography Techniques
- Molecular Junctions and Nanostructures
- Crystallization and Solubility Studies
- MicroRNA in disease regulation
- DNA and Biological Computing
McMaster University
2022-2024
Northwestern University
2018-2021
McGill University
2012-2019
We set out to design, synthesize, and optimize a DNA-minimal cage capable of encapsulating oligonucleotide drugs facilitate their delivery. Through rational design optimization using in vitro assays, we have assembled the first DNA "nanosuitcase" that can encapsulate siRNA construct release it upon recognition an trigger. The latter may be mRNA or microRNA (miRNA) which offers potential for dual synergistic therapy. This assembles near 100% yield, releases its cargo on demand, sustain...
DNA nanotubes hold promise as scaffolds for protein organization, templates of nanowires and photonic systems, drug delivery vehicles. We present a new DNA-economic strategy the construction with backbone produced by rolling circle amplification (RCA), which results in increased stability templated length. These are more resistant to nuclease degradation, capable entering human cervical cancer (HeLa) cells significantly uptake over double-stranded DNA, amenable encapsulation release...
Here, we demonstrate a new approach for the design and assembly of dynamic DNA cube with an addressable cellular uptake profile.
RNA-based therapeutics are emerging as a powerful platform for the treatment of multiple diseases. Currently, two main categories nucleic acid therapeutics, antisense oligonucleotides and small interfering RNAs (siRNAs), achieve their therapeutic effect through either gene silencing, splicing modulation or microRNA binding, giving rise to versatile options target pathogenic expression patterns. Moreover, ongoing research seeks expand scope drugs include more complex templates, such messenger...
Herein, a method for synthesizing and utilizing DNA dendrons to deliver biomolecules living cells is reported. Inspired by high-density nucleic acid nanostructures, such as spherical acids, we hypothesized that small clusters of in the form dendrons, could be conjugated facilitate their cellular uptake. We show are internalized 90% dendritic after just 1 h treatment, with >20-fold increase delivery per cell compared linear counterparts. This effect due interaction scavenger receptor-A on...
The translation of proteins as effective intracellular drug candidates is limited by the challenge cellular entry and their vulnerability to degradation. To advance therapeutic potential, cell-impermeable can be readily transformed into protein spherical nucleic acids (ProSNAs) densely functionalizing surfaces with DNA, yielding structures that are efficiently taken up cells. Because small structural changes in chemical makeup a conjugated ligand affect bioactivity associated protein,...
Increasing the polymer content on biosensors is important to improve sensor function by altering surface properties and increasing number of capture sites for analytes. Grafting-to methods are often employed but may be limited insufficient immobilization. Herein, we have utilized Graft-then-Shrink (GtS) simultaneously increase grafting-to surfaces produce low-cost, local plasmon resonance (LSPR) Au biosensors. The were incorporated within microwell plates, where translocation materials...
DNA intercalation has found many diagnostic and therapeutic applications. Here, we propose the use of simple intercalators, such as ethidium bromide, tools to facilitate error-free self-assembly nanostructures. We show that bromide can influence self-assembly, decrease formation oligomeric side products, cause libraries multiple equilibrating structures converge into a single product. Using variety 2D- 3D-DNA systems, demonstrate intercalators present powerful alternative for adjustment...
Two DNA-cross-linking reagents, bis-chloroethylnitrosourea and 8-methoxypsoralen, are used to covalently cross-link interstrand base pairs in DNA bonds that, part, define colloidal crystals engineered with DNA. The irreversible linkages formed increase the chemical thermal stability of do not significantly affect their long-range order, as evidenced by small-angle X-ray scattering data. post-modified stable environments that pre-modified structures not, including solvents encompass a broad...
Nanoparticles functionalized with DNA can assemble into ordered superlattices defined crystal habits through programmable "bonds". Here, we examine the interactions of multivalent cations these bonds as a chemical approach for actuating colloidal superlattices. Multivalent alter structure on molecular scale, enabling "bond length" to be reversibly altered between 17 and 3 nm, ultimately leading changes in overall dimensions micrometer-sized superlattice. The identity, charge, concentration...
A new method for synthesizing deoxynucleic guanidine (DNG) oligonucleotides that uses iodine as a mild and inexpensive coupling reagent is reported. This eliminates the need toxic mercury salts pungent thiophenol historically used in methods aimed at preparing DNG oligonucleotides. strategy was readily translated to standard MerMade 12 oligonucleotide synthesizer with yields of 95% has enabled synthesis 20-mer oligonucleotide, longest strand date, addition mixed DNA-DNG sequences 3-9...
In this report, we demonstrate the assembly of length-programmed DNA nanostructures using a single 16 base sequence and its complement as building blocks. To achieve this, applied Vernier mechanism to assembly, which uses mismatch in length between two monomers dictate final product. Specifically, approach relies on interaction strands containing different number (n, m) complementary binding sites: these will keep each other until they come into register, thus generating larger whose (n × is...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to Rolling Circle Amplification-Templated DNA Nanotubes Show Increased Stability and Cell Penetration AbilityGraham D. Hamblin, Karina M. Carneiro, Johans F. Fakhoury, Katherine E. Bujold, Hanadi Sleiman*Cite this: J. Am. Chem. Soc. 2012, 134, 11, 5426Publication Date (Web):March 13, 2012Publication History Published online13 March 2012Published inissue 21...
Abstract The ongoing COVID-19 pandemic has highlighted the need for innovative therapeutic strategies to combat rapidly evolving pathogens that challenge efficacy of traditional vaccines and monoclonal antibody treatments. Here, we explored potential TMSA52, a previously described homotrimeric DNA aptamer as universal prophylactic agent against SARS-CoV-2. TMSA52 demonstrates exceptional binding affinities broad neutralization diverse SARS-CoV-2 variant spike proteins are further enhanced...
Abstract This protocol describes a method based on iodine and base as mild coupling reagents to synthetize deoxyribonucleic guanidines (DNGs)—oligodeoxynucleotide analogues with guanidine backbone. DNGs display unique properties, such high cellular uptake low toxicity increased stability against nuclease degradation, but have been impeded in their development by the requirement for toxic iterative manual synthesis protocols. The novel reported here eliminates need mercuric chloride pungent...