What We Work On:

Combining Chemistry and Biology

Using our skills as chemists, we seek to develop new systems for diagnostics and drug delivery using the programmability and biocompatibility of DNA. We are currently working on projects to understand how DNA nanostructures behave in vivo.

Designing DNA-Minimal Architectures

Utilizing only a minimal set of DNA strands, we build unique 3D structures for uses in applications such as drug delivery and organization of other materials. This strategy allows us to make complex constructs using less DNA than other methods.

Expanding the DNA Toolbox

In the Sleiman lab, we work towards interfacing DNA with many other materials, including organic molecules, metal ions, and inorganic nanomaterials, to explore how DNA can be used to modify and organize these moieties. We also make sequence-defined polymers with DNA.

Combining Chemistry and Biology

The on-demand delivery of small molecules and nucleic acid-based therapeutics is of great interest to the medical community. Using our expertise in DNA assembly, we design and assemble nanostructures for drug delivery and diagnostic applications, including DNA micelles (ACS Appl. Mater. Interfaces 2019), nanotubes with hydrophobic pockets (Adv. Healthc. Mater. 2018), and DNA “nanosuitcases that carry siRNA (JACS 2016). We have also demonstrated the stabilization of DNA nanostructures in vivo by binding to human serum albumin (JACS 2017). 

In order for these materials to reach their full potential, however, we must also develop an understanding of their cellular uptake. We recently reported that intracellular fluorescence, and even FRET signals, cannot necessarily be correlated with the cellular uptake of intact DNA structures, highlighting the need for new methods to quantify the biological properties of DNA nanostructures, an area that we are actively working in. (ACS Cent. Sci. 2019) .

Designing DNA-Minimal Architectures

A major research focus in our laboratory is the construction of 3D DNA-minimal “wireframe” architectures that require far fewer unique DNA sequences than other methodologies. Using this approach, we showed the first modular synthesis of prismatic DNA cages with deliberate variation of size and geometry, and controlled size switching with added DNA strands (JACS 2007, ChemComm. 2011, JACS, 2012). We also reported DNA cages (Nat. Chem. 2013) and DNA nanotubes (Nat. Chem. 2015, ACS Nano 2013), where geometry, length (Nat. Commun. 2015) and dynamic character (ACS Nano 2015ACS Nano 2018) could be precisely varied and controlled. 

Additionally, we  developed a new approach to DNA construction, in which synthetic molecules control and modify DNA self-assembly (Science 2008, Chem. Soc. Rev. 2011, Nat. Rev. Mater. 2017).  

Expanding the DNA Toolbox

 Our group works towards expanding on the biological DNA “alphabet” of adenine, thymine, guanine, and cytosine. By interfacing DNA strands with inexpensive small molecules such as cyanuric acid, we have found that their assembly can be reprogrammed, generating fibrous structures (Nat. Chem. 2016). 

DNA structures can also be used as impermanent scaffolds to create programmable materials. Functioning as a molecular “printing press”, information contained in DNA architectures can be transferred onto gold nanoparticles that then become just as programmable as the original structure. (Nat. Chem. 2016) We recently applied the concept of DNA printing to synthetic polymers (Nat. Chem. 2018) and even small molecule (Angew. 2019)   further expanding the library of materials that can be encoded with DNA’s structural addressability.

Using solid-phase chemistry based on the phosphoramidite synthesis of DNA, we also develop new methods for the generation of sequence-defined polymers (J. Org. Chem 2018). By interfacing DNA with hydrophobic polymers, for example, new self-assembly properties can be accessed (JACS 2018JACS 2016).