About

Thomas Hermann is a professor in the Program in Materials Science and Engineering at UC San Diego. His research focuses on nucleic acid nanotechnology, specifically RNA-DNA hybrid nanostructures, and the development of synthetic methods for composite soft materials. His laboratory uses structure information to design RNA and hybrid nanostructures that self-assemble from small nucleic acid motifs, serving as platforms for functionalization. The Hermann lab was the first to characterize RNA nanostructures by X-ray crystallography. A key aspect of his work involves integrating additive and subtractive methods to enable precise fabrication of nucleic acid nanostructures with molecular features at the sub-10nm scale. Drawing inspiration from organic molecular synthesis, he approaches the preparation of these nanostructures as a multistep noncovalent transformation, harnessing the thermodynamics of self-assembly pathways to process information stored in the constituent modules toward creating complex architectures. Professor Hermann studied chemistry at the University of Ulm in Germany and performed graduate research at the Max-Planck Institute for Biochemistry in Martinsried. He earned his Ph.D. in biochemistry from Ludwig-Maximilians University in Munich in 1996. Following his doctoral studies, he worked as a postdoctoral researcher at the CNRS in Strasbourg, France, and at the Sloan-Kettering Cancer Center in New York. In 2005, he joined the Department of Chemistry and Biochemistry at UC San Diego, where he currently serves as a professor. Additionally, he is a founding director of the Center for Drug Discovery Innovation and has been serving as the Associate Dean for Education and Students in the School of Physical Sciences since 2018.

Research topics

• Biochemistry
• Chemistry
• Computational biology
• Computer Science
• Combinatorial chemistry
• Biophysics
• Biology
• Nanotechnology

Selected publications

• Metalated Nucleic Acid Nanostructures

  Methods in molecular biology · 2023-01-01

  articleSenior author
  PublisherDOI

• Nano-sandwich composite by kinetic trapping assembly from protein and nucleic acid

  Nucleic Acids Research · 2021-09-08 · 4 citations

  articleOpen accessSenior authorCorresponding

  Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA-DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein-RNA-DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.

  PublisherOA PDFDOI

• RNA–DNA Hybrid Nanoshape Synthesis by Facile Module Exchange

  Journal of the American Chemical Society · 2021 · 11 citations

  Senior authorCorresponding
  • Computer Science
  • Chemistry
  • Nanotechnology

  The preparation of nucleic acid nanostructures has relied predominantly on procedures of additive fabrication in which complex architectures are assembled by concerted self-assembly and sequential addition of building blocks. We had previously established RNA-DNA hybrid nanoshapes with modular architectures that enable multistep synthetic approaches inspired by organic molecular synthesis where additive and transformative steps are used to prepare complex molecular architectures. We report the establishment of module replacement and strand exchange as synthetic transformations in nucleic acid hybrid nanoshapes, which are enabled by minimally destabilizing sequence elements such as a single unpaired overhang nucleotide or a mismatch base pair. Module exchange facilitated by thermodynamic lability triggers adds a powerful transformative approach to the repertoire of additive and transformative synthetic methods for the preparation of complex composite materials.

  PublisherDOI

• A simple screening strategy for complex RNA-DNA hybrid nanoshapes

  Methods · 2021-02-23 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

• Syntheses and Binding Testing of N1-Alkylamino-Substituted 2-Aminobenzimidazole Analogues Targeting the Hepatitis C Virus Internal Ribosome Entry Site*

  Australian Journal of Chemistry · 2020-01-30 · 5 citations

  article

  A series of 2-aminobenzimidazole analogues have been synthesised and tested for binding to a previously established RNA target for viral translation inhibitors in the internal ribosome entry site (IRES) of the hepatitis C virus (HCV). Synthesis of new inhibitor compounds followed a highly convergent strategy which allowed for incorporation of diverse tertiary amino substituents in high overall yields (eight-steps, 4–22 %). Structure–activity relationship (SAR) studies focussed on the tertiary amine substituent involved in hydrogen bonding with the RNA backbone at the inhibitor binding site. The SAR study was further correlated with in silico docking experiments. Analogous compounds showed promising activities (half maximal effective concentration, EC50: 21–89 µM). Structures of the synthesised analogues and a correlation to their mode of binding, provided the opportunity to explore parameters required for selective targeting of the HCV IRES at the subdomain IIa which acts as an RNA conformational switch in HCV translation.

  PublisherDOI

• Complex RNA-DNA hybrid nanoshapes from iterative mix-and-match screening

  Nano Research · 2020-09-21 · 5 citations

  articleSenior authorCorresponding

  Hybrid nucleic acid nanostructures partition architectural and functional roles between ribonucleic acid (RNA) joints and deoxyribonucleic acid (DNA) connectors. Nanoshapes self-assemble from nucleic acid modules through synergistic stabilization of marginally stable base pairing interactions within circularly closed polygons. Herein, we report the development of hybrid nanoshapes that include multiple different RNA modules such as internal loop and three-way junction (3WJ) motifs. An iterative mix-and-match screening approach was used to identify suitable DNA connectors that furnished stable nanoshapes for combinations of different RNA modules. The resulting complex multicomponent RNA-DNA hybrid nanoshapes were characterized by atomic force microscopy (AFM) imaging. Our research provides proof of concept for modular design, assembly and screening of RNA-DNA hybrid nanoshapes as building blocks for complex extended nucleic acid materials with features at the sub-10 nm scale.

  PublisherDOI

• Editorial Overview: Nanobiotechnology

  Current Opinion in Biotechnology · 2020-06-01

  editorialSenior author
  PublisherDOI

• RNA–DNA hybrid nanoshapes that self-assemble dependent on ligand binding

  Nanoscale · 2020 · 11 citations

  Senior authorCorresponding
  • Chemistry
  • Computational biology
  • Biophysics

  Self-assembly of nucleic acid nanostructures is driven by selective association of oligonucleotide modules through base pairing between complementary sequences. Herein, we report the development of RNA-DNA hybrid nanoshapes that conditionally assemble under the control of an adenosine ligand. The design concept for the nanoshapes relies on ligand-dependent stabilization of DNA aptamers that serve as connectors between marginally stable RNA corner modules. Ligand-dependent RNA-DNA nanoshapes self-assemble in an all-or-nothing process by coupling adenosine binding to the formation of circularly closed structures which are stabilized through continuous base stacking in the resulting polygons. By screening combinations of various DNA aptamer constructs with RNA corner modules for the formation of stable complexes, we identified adenosine-dependent nanosquares whose shape was confirmed by atomic force microscopy. As a proof-of-concept for sensor applications, adenosine-responsive FRET-active nanosquares were obtained by dye conjugation of the DNA aptamer components.

  PublisherDOI

• Versatile kit of robust nanoshapes self-assembling from RNA and DNA modules

  Nature Communications · 2019-02-05 · 47 citations

  articleOpen accessSenior authorCorresponding

  DNA and RNA have emerged as a material for nanotechnology applications that take advantage of the nucleic acids' ability to encode folding and programmable self-assembly through mainly base pairing. The two types of nucleic acid have rarely been used in combination to enhance structural diversity or for partitioning of functional and architectural roles. Here, we report a design and screening strategy to integrate combinations of RNA motifs as architectural joints and DNA building blocks as functional modules for programmable self-assembly of a versatile toolkit of polygonal nucleic acid nanoshapes. Clean incorporation of diverse DNA modules with various topologies attest to the extraordinary robustness of the RNA-DNA hybrid framework. The design and screening strategy enables systematic development of RNA-DNA hybrid nanoshapes as programmable platforms for applications in molecular recognition, sensor and catalyst development as well as protein interaction studies.

  PublisherOA PDFDOI

• Design and Crystallography of Self-Assembling RNA Nanostructures

  Methods in molecular biology · 2017-01-01 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R01AI072012

  NIH · $1.8M · 2012

• NIH Grant R44AI051104

  NIH · $1.2M · 2006

• Self-Assembling RNA Nanosensors

  NSF · $337k · 2016–2019

• Responsive materials from self-assembling nucleic acid nanoshapes

  NSF · $535k · 2021–2025

• NIH Grant R01CA132753

  NIH · $1.6M · 2014

Frequent coauthors

• Sergey M. Dibrov

  University of California, San Diego

  33 shared

• Mark A. Boerneke

  University of North Carolina at Chapel Hill

  17 shared

• Klaus B. Simonsen

  Lundbeck (Denmark)

  14 shared

• Qiang Zhao

  Peking University Cancer Hospital

  12 shared

• Dionisios Vourloumis

  National Centre of Scientific Research "Demokritos"

  12 shared

• Jerod Parsons

  Tempus Labs (United States)

  10 shared

• Benjamin K. Ayida

  10 shared

• Kevin D. Rynearson

  University of California, San Diego

  10 shared

Education

• Ph.D., biochemistry

  Ludwig-Maximilians University in Munich

  1996

• M.S.

  Max-Planck Institute for Biochemistry

• B.S., chemistry

  University of Ulm