Lab

Hanadi F Sleiman's Lab

Featured projects (1)

Featured research (4)

The self-assembly of block copolymers is often rationalized by structure and microphase separation; pathways that diverge from this parameter space may provide new mechanisms of polymer assembly. Here, we show that the sequence and length of single-stranded DNA directly influence the self-assembly of sequence-defined DNA block copolymers. While increasing the length of DNA led to predictable changes in self-assembly, changing only the sequence of DNA produced three distinct structures: spherical micelles (spherical nucleic acids, SNAs) from flexible poly(thymine) DNA, fibers from semirigid mixed-sequence DNA, and networked superstructures from rigid poly(adenine) DNA. The secondary structure of poly(adenine) DNA strands drives a temperature-dependent polymerization and assembly mechanism: copolymers stored in an SNA reservoir form fibers after thermal activation, which then aggregate upon cooling to form interwoven networks. DNA is often used as a programming code that aids in nanostructure addressability and function. Here, we show that the inherent physical and chemical properties of single-stranded DNA sequences also make them an ideal material to direct self-assembled morphologies and select for new methods of supramolecular polymerization.
DNA tweezers have emerged as powerful devices for a wide range of biochemical and sensing applications; however, most DNA tweezers consist of single units activated by DNA recognition, limiting their...
Conjugation of lipid moieties to nucleic-acid therapeutics increases their interaction with cellular membranes, enhances their uptake and influences in vivo distribution. Once injected in biological fluids, such modifications trigger the binding of various serum proteins, which in turn play a major role in determining the fate of oligonucleotides. Yet, the role played by each of these proteins, more than 300 in serum, remains to be elucidated. Albumin, the most abundant circulating protein is an attractive candidate to study, as it was previously used to enhance the therapeutic effect of various drugs. Herein, we present a thorough fluorescent-based methodology to study the effect of strong and specific albumin-binding on the fate and cellular uptake of DNA oligonucleotides. We synthesized a library of molecules that exhibit non-covalent binding to albumin, with affinities ranging from high (nanomolar) to none. Our results revealed that strong albumin binding can be used as a strategy to reduce degradation of oligonucleotides in physiological conditions caused by enzymes (nucleases), to reduce uptake and degradation by immune cells (macrophages) and to prevent non-specific uptake by cells. We believe that introducing protein-binding domains in oligonucleotides can be used as a strategy to control the fate of oligonucleotides in physiological environments. While our study focuses on albumin, we believe that such systematic studies, which elucidate the role of serum proteins systematically, will ultimately provide a toolbox to engineer the next-generation of therapeutic oligonucleotides, overcoming many of the barriers encountered by these therapeutics, such as stability, immunogenicity and off-target effects.
Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to typically low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker recognition properties and as stimuli, notably in amplified small molecule release via nucleic acid‐templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo . Here, we report the first use the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We first couple HCR with a DNA‐templated reaction resulting in the amplified, immolative release of small molecules. Moreover, we integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. Overall, this work translates the amplification of HCR into small molecule release without the use of multiple components, and will aid its application to biosensing, imaging and drug delivery.

Lab head

Hanadi F Sleiman
Department
  • Department of Chemistry

Members (21)

Anthony K Mittermaier
  • McGill University
Violeta Toader
  • McGill University
Felix Rizzuto
  • UNSW Sydney
Karina M M Carneiro
  • University of Toronto
Johans J Fakhoury
  • McGill University
Empar Vengut-Climent
  • University of Valencia
Amine Garci
  • Northwestern University
Katherine J Castor
  • McGill University
Chantal Autexier
Chantal Autexier
  • Not confirmed yet
Johans Fakhoury
Johans Fakhoury
  • Not confirmed yet
Philippe Dauphin-Ducharme
Philippe Dauphin-Ducharme
  • Not confirmed yet
Donatien de Rochambeau
Donatien de Rochambeau
  • Not confirmed yet
Danny Bousmail
Danny Bousmail
  • Not confirmed yet