Research

The Bathe BioNanoLab engineers programmable materials made from DNA and RNA. By treating nucleic acids not only as genetic molecules but as a construction material, we design nanoscale structures with atomic precision to address major challenges in medicine, energy, computation, and information storage. In medicine, we develop nucleic acid–based systems for targeted delivery of mRNA, ASO, siRNA, and CRISPR therapeutics, and we design virus-mimicking active immunotherapy platforms that enhance immune protection against progressive and infectious diseases. Beyond healthcare, we use DNA to precisely organize functional materials—such as quantum dots and molecular chromophores—to enable new approaches to quantum photonics and quantum information processing. Our work also advances molecular data storage and ambient-temperature biobanking, aiming to reduce cold-chain dependence and expand global access to genomic and digital information. Across these diverse efforts, our mission is unified: to harness the programmability of biology to build new technologies with societal impact. These revolutionary applications of nucleic acid nanotechnology are discussed below in more detail.

Please see here for a recent presentation from Prof. Bathe on the lab’s work.

Structural nucleic acid Nanotechnology

DNA is best known as the molecule that carries our genetic code. But it is also an extraordinary building material. Because its sequence can be precisely programmed, DNA can be folded and assembled into intricate two- and three-dimensional structures at the nanometer scale—thousands of times smaller than the width of a human hair. Using this molecular “construction kit,” we design and build complex nanoscale architectures that can organize other functional materials with atomic precision. These include virus-like particles for vaccines and targeted drug delivery, light-harvesting systems that arrange dye molecules for efficient nanoscale energy transport, and precisely positioned quantum dots for sensing and emerging quantum technologies. For perspective, the icosahedral DNA particle shown here is about 40 nanometers across. Each edge is formed by a DNA double helix just 2 nanometers in diameter—while a human hair measures roughly 10,000 to 100,000 nanometers thick. By programming matter at this scale, we can create entirely new classes of materials with applications in medicine, energy, and information technology.

Virus-like Particles for therapeutic delivery and Active Immunotherapies

Natural viruses are remarkably efficient biological machines. Proteins on their outer surface allow them to enter specific cells, evade immune defenses, and deliver genetic material into the body. We draw inspiration from these capabilities—without using infectious components—to build structured DNA and RNA nanoparticles that mimic key features of viruses in a safe, programmable way. These “virus-like” particles can be engineered for two complementary purposes.

First, they can serve as precision delivery vehicles. By programming their size, shape, and surface chemistry, we design nanoparticles that transport therapeutic siRNA, mRNA, or CRISPR gene editors to specific organs and tissues—including the central nervous system. This work aims to expand treatment options for neurological disorders, genetic diseases, and cancer by enabling targeted molecular therapies in the brain and other difficult-to-reach tissues.

Second, we use these same programmable particles as active immunotherapies. By displaying multiple copies of carefully selected proteins or peptides on their surface, the particles stimulate the body’s humoral immune system to generate protective antibodies. This approach supports vaccine development not only against infectious diseases such as HIV, but also against central nervous system disorders such as Alzheimer’s disease, where inducing antibodies against pathological protein aggregates represents a promising therapeutic strategy.

The DNA-based particle shown here carries 10 copies of a target antigen arranged with nanometer precision (scale bar: 10 nm). By controlling antigen number, spacing, and geometry, we can tune immune activation in ways that are not possible with conventional vaccine platforms.

Together, this work harnesses the programmability of nucleic acids to create safe, modular systems for both targeted gene delivery and antibody-inducing immunotherapies, bridging nanotechnology and medicine at the molecular scale.

Quantum INFORMATION PROCESSING

Natural photosynthetic complexes consist of densely packed arrays of chlorophyll molecules that facilitate photon adsorption and energy transfer for the production of the chemical fuel ATP, which is the origin of energy for life on planet earth. Programmed self-assembly of synthetic DNA into precise 2D and 3D nanoscale architectures that mimic natural light-harvesting systems can now be used to organize chromophores to replicate key aspects of bacterial photosynthetic systems, controlling how energy and quantum information are transported at the nanoscale. In this research, we are fabricating structured DNA assemblies with embedded chromophores to understand how to efficiently harness energy from the sun, as well as engineer new qubits—the computing unit of quantum computers—that operate at room temperature. (Figure is courtesy Ella Maru Studio.)

Molecular Computing, Data Storage & Retrieval

The 4-letter ATGC code of DNA in our cells encodes approximately 1 gigabyte of information per human genome, packaged up neatly within the nucleus of the cell. Synthetic DNA can similarly be used as a storage medium to contain files and other data in an extremely compact manner such that the entire world’s information could in principle fit in the palm of our hand if encoded in DNA. However, retrieving information or files from such “pools” of data encoded in DNA is a highly non-trivial task, since this information is in principle unstructured and disorganized. An analogy would be finding a page or chapter from a book in the US Library of Congress if all of its books were simply piled into the center of a football stadium. In this research area our lab is using DNA nanoparticles to organize and structure data and information stored in DNA, and developing ways to both randomly access arbitrary pools of data ranging from 1 MB to 1 GB from a pool of 1 Exabyte of data (1 Exabyte is 1 billion GB), as well as to compute using these molecular datasets, ranging from machine learning to data sorting and image recognition. Figure from Scientific American.

profiling neurons to understand Mutations associated with Autism

Genetic studies have now revealed dozens of mutations associated with autism spectrum disorder (ASD) that affects approximately 1 in 36 children in the US alone. The majority of these mutations are associated with neuronal synapse proteins, which regulate signal transmission in the brain. In order to develop successful therapeutics to treat ASD, it is therefore essential to understand how these mutations impact neuronal synapse structure and function, and ideally in patient-derived neuronal samples from induced pluripotent stem cells. Toward this end we are developing highly multiplexed fluorescence imaging of neuronal synapse proteins, mRNAs, and neuronal activity to offer deep, multimodal profiling of neuronal synapse structure and function with barcoded nucleic acid imaging probes. This neuronal profiling platform will enable downstream discovery of new therapeutics to treat ASD, as well as other neurodevelopmental diseases and disorders such as schizophrenia.

programming custom rna catalysts

RNAs perform a variety of important roles in cells, from acting as trans regulators (e.g. siRNA and lncRNA) of many cellular processes to catalyzing peptide bond formation in the ribosome. The tertiary structure of RNA plays a critical role in its binding and catalytic function, which is extremely challenging to predict or engineer. In this research area we are using programmed nucleic acid assemblies to coordinate synthetic RNA sequences to endow them with catalytic properties de novo, or that replicate and improve on existing enzymes such as the ribosome. This research will ultimately enable cell-free production of materials and chemicals using custom RNA-based enzymes.