Nyerges Lab

Our lab at Harvard Medical School works at the interface of directed evolution, synthetic genomics, and protein engineering. We rewrite genomes and reassign codons to equip engineered cells with functions inaccessible to natural organisms: complete resistance to natural viruses, escape-free containment of cells and their transgenes, and ribosomal synthesis of polymers, peptides, and biologic drugs with chemistries beyond the canonical amino-acid alphabet.

We are exploring how the genetic code can be radically rewritten — establishing genetic firewalls that make engineered cells resistant to all natural viruses and biocontain their genetic information from the natural ecosystem — and harnessing these advances for drug discovery and delivery. We strive to translate our findings and technologies into next-generation therapeutics and secure biotechnologies.

Three research directions

Expanding ribosomal chemistry. We develop genetic code engineering technologies — orthogonal aminoacyl-tRNA synthetase/tRNA pairs, engineered translation systems, and genomes to host these — that enable site-specific incorporation of noncanonical monomers, enabling the biological production and directed evolution of peptide therapeutics, sequence-defined polymers, and enzymes with chemistries inaccessible to canonical translation.

Escape-free biocontainment of engineered organisms and their genetic information. Genetically modified (micro)organisms share the canonical genetic code with all natural life, enabling engineered strains — and their engineered genetic information — to spread into natural microbiomes through proliferation and horizontal gene transfer. We construct genetic-code-based firewalls to block escape in which (i) the survival of engineered cells is linked to exogenously supplied noncanonical amino acids not available in nature, and (ii) their engineered genes are rendered uninterpretable to any organism that acquires them. This program is supported by our NIH/NIBIB award. Our long-term aim is noninvasive, in vivo drug production.

Mining nature’s genetic code engineering toolkit. Although the canonical code is remarkably conserved, billions of years of evolution have explored numerous alternatives. Building on our discovery of how viral tRNAs reprogram the genetic code and their superior performance over their cellular counterparts in genetic code engineering, we mine nature for new ways to engineer the genetic code and produce protein drugs.

Multidisciplinary approach

We integrate genome synthesis, directed evolution, multi-omics (proteomics, transcriptomics, ribosome profiling), machine learning, structural biology, and computational protein design to engineer biology at the genome scale and to access functions new to nature.

More about our research, recent publications, and news.