The Codon Guide to Synthetic Biology
Books, papers, courses, and blogs to help you get started.
Last edit: 13 September 2023
Progress in biology is arguably moving faster today than at any point in the course of human history. Engineered biology has profound potential to change how we live, but the field has become broad, bloated, nebulous. It can feel overwhelming just to keep up, let alone enter the subject, grasp its core ideas, or contribute to its improvement.
The first step to mastering a subject is to start…somewhere. And the best way to find that somewhere, often, is with a guide. So I spent the last week scouring the web and racking my brain for useful resources on synthetic biology. Consider this your “start” on a (hopefully) long and fulfilling intellectual journey.
This guide is a living document. Please send suggestions and additions to my email. I gratefully acknowledge others who have compiled similar resources, including Michael Retchin, Roberto Solari, Alex Telford, and Pillar VC.
📙 Seminal Papers to Get You Up to Speed
Mostly open-access; some are paywalled. → means “start here.”
Foundations
Basics of Synthetic Biology
→Foundations for engineering biology, by Endy D. Nature (2005). Link
→A brief history of synthetic biology, by Cameron D.E. et al. Nature Reviews Microbiology (2014). Link
Synthetic biology: applications come of age, by Khalil A.S. & Collins J.J. Nature Reviews Genetics (2010). Link
Is the cell really a machine?, by Nicholson D.J. Journal of Theoretical Biology (2019). Link
The second wave of synthetic biology: from modules to systems, by Purnick P.E.M. & Weiss R. Nature Reviews Molecular Cell Biology (2009). Link
The second decade of synthetic biology: 2010–2020, by Meng F. & Ellis T. Nature Communications (2020). Link
Synthetic biology in mammalian cells: next generation research tools and therapeutics, by Lienert F. et al. Nature Reviews Molecular Cell Biology (2014). Link
The Central Dogma
→60 years ago, Francis Crick changed the logic of biology, by Cobb M. PLoS Biology (2017). Link
The Elaboration of the Central Dogma. Scitable, by Nature Education. Link
Central dogma at the single-molecule level in living cells, by Li G-W. & Xie X.S. Nature (2011). Link
Gene Expression & Regulation
→Genetic regulatory mechanisms in the synthesis of proteins, by Jacob F. & Monod J. Journal of Molecular Biology (1961). Link (Explained).
Gene Expression and Regulation. Scitable, by Nature Education. Link
A Unified Theory of Gene Expression, by Orphanides G. & Reinberg D. Cell (2002). Link
Precise and reliable gene expression via standard transcription and translation initiation elements, by Mutalik V.K. et al. Nature Methods (2013). Link
Biological Networks & Mathematics
→Network motifs in the transcriptional regulation network of Escherichia coli, by Shen-Orr S.S. et al. Nature Genetics (2002). Link
Modelling and analysis of gene regulatory networks, by Karlebach G. & Shamir R. Nature Reviews Molecular Cell Biology (2008). Link
Artificial Gene Regulatory Networks—A Review, by Cussat-Blanc S. et al. Artificial Life (2018). Link
Mathematical modeling and synthetic biology, by Chandran D. et al. Drug Discovery Today: Disease Models (2008). Link
Graphic Notations
→Synthetic Biology Open Language Visual: An Open-Source Graphical Notation for Synthetic Biology, by Quinn J. et al. Link
The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology, by Galdzicki M. et al. Nature Biotechnology (2014). Link
The Systems Biology Graphical Notation, by Le Novère N. et al. Nature Biotechnology (2009). Link
Technologies
DNA Sequencing
→DNA sequencing at 40: past, present and future, by Shendure J. Nature (2017). Link
DNA Cost and Productivity Data, aka "Carlson Curves", by Carlson R. Synthesis.cc (2022). Link
Next-Generation DNA Sequencing Methods, by Mardis E.R. Annual Review of Genomics and Human Genetics. (2008). Link
DNA Synthesis
→Large-scale de novo DNA synthesis: technologies and applications, by Kosuri S. & Church G.M. (2014). Link
DNA synthesis technologies to close the gene writing gap, by Hoose et al. (2023). Link
Synthetic DNA Synthesis and Assembly: Putting the Synthetic in Synthetic Biology, by Hughes R.A. & Ellington A.D. Cold Spring Harbor Perspectives in Biology. Link
Deoxynucleoside phosphoramidites—A new class of key intermediates for deoxypolynucleotide synthesis, by Beaucage S.L. & Caruthers M.H. Tetrahedron Letters (1981). Link
Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process, by LeProust E.M. et al. Nucleic Acids Research (2010). Link
De novo DNA synthesis using polymerase-nucleotide conjugates, by Palluk S. et al. Nature Biotechnology (2018). Link
DNA Assembly
→Bricks and blueprints: methods and standards for DNA assembly, by Casini A. et al. Nature Reviews Molecular Cell Biology (2015). Link
Recent advances in DNA assembly technologies, by Chao R. et al. FEMS Yeast Research (2015). Link
BglBricks: A flexible standard for biological part assembly, by Anderson J.C. et al. Journal of Biological Engineering (2010). Link
Enzymatic assembly of DNA molecules up to several hundred kilobases, by Gibson D.G. et al. Nature Methods (2009). Link (Gibson assembly)
A Modular Cloning System for Standardized Assembly of Multigene Constructs, by Weber E. et al. PLoS One. (2011). Link (Golden Gate assembly)
Other Basic Methods & Cloning
→Basic Methods in Cellular and Molecular Biology, by multiple authors. JoVE. Link
→DNA cloning: A personal view after 40 years, by Cohen S.N. PNAS (2013). Link
Molecular Cloning Techniques, by AddGene. Link
Isolating, Cloning, and Sequencing DNA, by Alberts B. et al. Molecular Biology of the Cell, 4th Edition. Link
CRISPR-Cas
→CRISPR-Cas: biology, mechanisms and relevance, by Hille F. & Charpentier E. Philosophical Transactions of the Royal Society B (2016). Link
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity, by Jinek M. et al. (2012). Link
CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity, by Chen J.S. et al. Science (2018). Link
Nucleic acid detection with CRISPR-Cas13a/C2c2, by Gootenberg J.S. et al. Science (2017). Link
The next generation of CRISPR–Cas technologies and applications, by Pickar-Oliver A. & Gersbach C.A. (2019). Link
Base Editing
→Base editing: precision chemistry on the genome and transcriptome of living cells, by Rees H.A. & Liu D.R. (2018). Link
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage, by Komor A.C. et al. (2016). Link
Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage, by Gaudelli N.M. et al. (2017). Link
Prime Editing
→Prime editing for precise and highly versatile genome manipulation, by Chen P.J. & Liu D.R. Nature Reviews Genetics. (2022). Link
Search-and-replace genome editing without double-strand breaks or donor DNA, by Anzalone A.V. et al. (2019). Link
Directed Evolution
→Exploring protein fitness landscapes by directed evolution, by Romero P.A. & Arnold F.H. Nature Reviews Molecular Cell Biology (2009). Link
Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide, by Chen K. & Arnold F.H. PNAS (1993). Link
Methods for the directed evolution of proteins, by Packer M.S. & Liu D.R. Nature Reviews Genetics (2015). Link
Protein Structure Prediction & Design
→Advances in protein structure prediction and design, by Kuhlman B. & Bradley P. Nature Reviews Molecular Cell Biology (2019). Link
→A Brief History of De Novo Protein Design: Minimal, Rational, and Computational, by Woolfson D.N. Journal of Molecular Biology (2021). Link
The coming of age of de novo protein design, by Huang P-S. et al. Nature (2016). Link
Highly accurate protein structure prediction with AlphaFold, by Jumper J. et al. Nature (2021). Link (See the blog by Mohammed AlQuraishi.)
Genome Synthesis
→Synthetic Genomes, by Zhang W. et al. Annual Review of Biochemistry (2020). Link
Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome, by Gibson D.G. et al. Science (2010). Link
One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome, by Gibson D.G. et al. PNAS (2008). Link
Construction of a synthetic Saccharomyces cerevisiae pan-genome neo-chromosome, by Kutyna D.R. et al. Nature Communications (2022). Link (See this blog about the synthetic yeast project.)
Design and synthesis of a minimal bacterial genome, by Hutchison C.A. et al. Science (2016). Link
Defining synonymous codon compression schemes by genome recoding, by Wang K. et al. Nature (2016). Link
Applications
Biomaterials
→The living interface between synthetic biology and biomaterial design, by Liu A.P. et al. Nature Materials (2022). Link
Biological Engineered Living Materials: Growing Functional Materials with Genetically Programmable Properties, by Gilbert C. & Ellis T. ACS Synthetic Biology. Link
Wearable materials with embedded synthetic biology sensors for biomolecule detection, by Nguyen P.Q. et al. Nature Biotechnology (2021). Link
Regulating synthetic gene networks in 3D materials, by Deans T.L. et al. PNAS (2012). Link
Biosecurity & Biocontainment
→Building biosecurity for synthetic biology, by Trump B.D. et al. Molecular Systems Biology (2020). Link
Mitigating catastrophic biorisks, by Esvelt K. Effective Altruism. Link
Rational Design of Evolutionarily Stable Microbial Kill Switches, by Stirling F. et al. Molecular Cell (2017). Link
Synthetic biology approaches to biological containment: pre-emptively tackling potential risks, by Torres L. et al. Essays in Biochemistry (2016). Link
Benchtop DNA printers are coming soon—and biosecurity experts are worried, by Service R.F. Science (2023). Link
Biocontainment of genetically modified organisms by synthetic protein design, by Mandell D.J. et al. Nature (2015). Link
What rough beast? Synthetic biology, uncertainty, and the future of biosecurity, by Mukunda G. et al. Politics and the Life Sciences (2009). Link
Biosensors
→Synthetic Biology Enables Programmable Cell-Based Biosensors, by Hicks M. et al. ChemPhysChem (2019). Link
Cell-free biosensors for rapid detection of water contaminants, by Jung J.K, et al. Nature Biotechnology (2020). Link
Arsenic biosenseor: a step further, by French C. et al. BMC Systems Biology (2007). Link
Paper-Based Synthetic Gene Networks, by Pardee K. et al. Cell (2014). Link
Cell-Free Systems
→Synthetic Biology Goes Cell-Free, by Tinafar A. et al. BMC Biology (2019). Link
Cell-free gene expression, by Garenne D. et al. Nature Reviews Methods Primers (2021). Link
Cell-free gene expression: an expanded repertoire of applications, by Silverman A.D. et al. Nature Reviews Genetics (2019). Link
The PURE system for the cell-free synthesis of membrane proteins, by Kuruma Y. & Ueda T. Nature Protocols (2015). Link
An integrated cell-free metabolic platform for protein production and synthetic biology, by Jewett M.C. et al. Molecular Systems Biology (2008). Link
In vitro integration of ribosomal RNA synthesis, ribosome assembly, and translation, by Jewett M.C. et al. Molecular Systems Biology (2013). Link
Portable, On-Demand Biomolecular Manufacturing, by Pardee K. et al. Cell (2016). Link
Gene Circuits
→Principles of genetic circuit design, by Brophy J.A.N. & Voigt C.A. (2014). Link
Understanding Biological Regulation Through Synthetic Biology, by Bashor C.J. & Collins J.J. (2018). Link
Designing Biological Circuits: Synthetic Biology Within the Operon Model and Beyond, by English M.A. et al. Annual Review of Biochemistry (2021). Link
A synthetic oscillatory network of transcriptional regulators, by Elowitz M.B. & Leibler S. Nature (2000). Link
Construction of a genetic toggle switch in Escherichia coli, by Gardner T.S. et al. Nature (2000). Link
Engineering stability in gene networks by autoregulation, by Becskei A. & Serrano L. Nature (2000). Link
Engineering Escherichia coli to see light, by Levskaya A. et al. Nature (2005). Link (Explained).
Genetic programs constructed from layered logic gates in single cells, by Moon T.S. et al. Nature (2012). Link
Programmable single-cell mammalian biocomputers, by Ausländer S. et al. Nature (2012). Link
Gene Drives
→Gene Drives on the Horizon, by the National Academies (2016). Link
Genetic Control of Mosquitoes, by Alphey L. Annual Review of Entomology (2014). Link
Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi, by Gantz V.M. et al. PNAS (2015). Link
Regulating gene drives, by Oye K.A. et al. Science (2014). Link
Current CRISPR gene drive systems are likely to be highly invasive in wild populations, by Noble C. et al. eLife (2018). Link
Engineered Microbial Communities
→Synthetic Biology Tools to Engineer Microbial Communities for Biotechnology, by McCarty N.S. & Ledesma-Amaro R. (2018). Link
Engineering microbial consortia: a new frontier in synthetic biology, by Brenner et al. (2008). Link
Emergent cooperation in microbial metabolism, by Wintermute E.H. & Silver P.A. Molecular Systems Biology (2010). Link
Syntrophic exchange in synthetic microbial communities, by Mee M.T. et al. (2014). Link
Metabolic Engineering
→Metabolic Engineering: Past and Future, by Woolston B.M. et al. Annual Review of Chemical and Biomolecular Engineering (2013). Link
Physiological limitations and opportunities in microbial metabolic engineering, by López et al. Nature Reviews Microbiology (2021). Link
Production of the antimalarial drug precursor artemisinic acid in engineered yeast, by Ro D-K. et al. Nature (2006). Link
Tuning genetic control through promoter engineering, by Alper H. et al. PNAS (2005). Link
Microbial production of fatty-acid-derived fuels and chemicals from plant biomass, by Steen E.J. et al. Nature (2010). Link
Complete biosynthesis of opioids in yeast, by Galanie S. et al. Science (2015). Link
Carbon-negative production of acetone and isopropanol by gas fermentation at industrial pilot scale, by Liew F.E. et al. Nature Biotechnology (2022). Link
Plant Engineering
→Plant synthetic biology, by Liu W. & Stewart Jr. C.N. Trends in Plant Science (2015). Link
Synthetic genetic circuits as a means of reprogramming plant roots, by Brophy J.A.N. et al. Science (2022). Link
Quantitative characterization of genetic parts and circuits for plant synthetic biology, by Schaumberg K.A. et al. Nature Methods (2016). Link
Recoded Genomes
→Reprogramming the genetic code, by de la Torre D. & Chin J.W. Nature Reviews Genetics (2020). Link
Synthetic Genome Recoding: New genetic codes for new features, by Kuo J. et al. Current Genetics (2017). Link
An expanded genetic code with a functional quadruplet codon, by Anderson J.C. et al. PNAS (2004). Link
Sense codon reassignment enables viral resistance and encoded polymer synthesis, by Robertson W.E. et al. Science (2021). Link
A swapped genetic code prevents viral infections and gene transfer, by Nyerges A. et al. Nature (2023). Link
Total synthesis of Escherichia coli with a recoded genome, by Fredens J. et al. Nature (2019). Link
Synthetic Cells
→Progress Toward Synthetic Cells, by Blain J.C. & Szostak J.W. Annual Review of Biochemistry (2014). Link
Towards a synthetic cell cycle, by Olivi L. et al. Nature Communications (2021). Link
Reconstitution of ribosome self-replication outside a living cell, by Kosaka Y. et al. bioRxiv (2022). Link
Transmembrane transport in inorganic colloidal cell-mimics, by Xu Z. et al. Nature (2021). Link
Programmable Fusion and Differentiation of Synthetic Minimal Cells, by Gaut N.J. et al. ACS Synthetic Biology (2022). Link
📙 Courses
* = Recommended
What is Synthetic Biology? (EBRC)
*Introduction to Bioengineering (Stanford)
The Great Ideas of Biology (Caltech)
Engineering Life: Synbio, Bioethics & Public Policy (Johns Hopkins)
*Biological Circuit Design (Caltech)
Cellular Design Principles (Purdue)
Quantitative Microbiology (UCSD)
Miscellaneous methods and lectures (CSBERG)
*Physical Biology of the Cell (Caltech)
📚 Textbooks & Guides
(Recommended order. * = free.)
The Machinery of Life (a gentle introduction to the beauty of a cell.)
*Cell Biology by the Numbers (get a grasp for the numbers of biology.)
See the accompanying YouTube course by Ron Milo.
Use the Bionumbers database while doing your own calculations.
*Molecular Biology of the Cell
Pay close attention to sections on the Central Dogma and metabolic pathways.
Synthetic Biology - A Primer (Revised Edition) and BioBuilder
*Underground Garden Club (get hands-on practice.)
*CRISPRpedia (online textbook about CRISPR.)
(optional) A Computer Scientist's Guide to Cell Biology
Physical Biology of the Cell (a deep dive into biophysics.)
*Deep learning (see the accompanying computational biology course at MIT.)
📹 Video Channels
The Thought Emporium | Julia Bauman | Axial | The Sheekey Science Show | iBiology (Synthetic Biology series) | Foresight Institute | EBRC | Synthetic Biology One | Innovative Genomics Institute | Oral History of Agricultural Genetic Engineering
🔖 Books
Genentech: The Beginnings of Biotech, by Sally Smith Hughes
Invisible Frontiers: The Race to Synthesize a Human Gene, by Stephen S. Hall
The Eighth Day of Creation, by Horace Freeland Judson
Regenesis, by George Church & Ed Regis
The Genesis Machine, by Amy Webb & Andrew Hessel
The Gene: An Intimate History, by Siddhartha Mukherjee
Life at the Speed of Light, by J. Craig Venter
Higher Animals: Vaccines, Synthetic Biology, and the Future of Life, by Michael Specter
What’s Your Bio Strategy?, by John Cumbers & Karl Schmieder
A Crack in Creation, by Jennifer Doudna & Samuel Sternberg
The Double Helix, by James Watson
The Emergence of Life: From Chemical Origins to Synthetic Biology, by Pier Luigi Luisi
Bio Design: Nature + Science + Creativity, by William Myers
The Song of the Cell, by Siddhartha Mukherjee
Synthetic: How Life Got Made, by Sophia Roosth
The Singularity is Near, by Ray Kurzweil
✒️ Blogs & Original Essays
Codon (oh yeah) | Works in Progress | Asterisk Magazine | Decoding Bio | Asimov Blog | GROW Magazine | Biodecoded | The Century of Biology | Where Tech Meets Bio | Nucleate Signal | Sofia Sanchez | Sam Rodriques | In the Pipeline | Erika’s Newsletter | Biodraft_ | Positive Selection | Biocene Thoughts | Bowtied Biotech | Biomarker | The Glimpse | White Pill | Axial | a16z Blog | Future | Trevor Klee | Milky Eggs | Adaobi | Synthego Blog | Nintil | De Novo | Y Combinator | The Cell + Gene Curator | Twist Biosciences Blog | James Somers | Some Thoughts on a Mysterious Universe | Markov.bio
🎧 Podcasts
Grow Everything | SciBetter | Built with Biology | The Long Run with Luke Timmerman | Translation Podcast | The Readout Loud | The Bio Report | BioCentury This Week | Lady Scientist Podcast | Axial Podcast | Nature Podcast | Bio Eats World
🗞️ Journals
These are the journals that I check each week to find new papers. * = preferred.
*Nature Communications | PNAS | Current Biology | Synthetic Biology | Nucleic Acids Research | PLOS One (see the Synthetic Biology category) | PLOS Computational Biology | Nature Protocols | *Nature Biotechnology | Nature Chemical Biology | *Science | *Science Advances | ACS Synthetic Biology | *Nature | Journal of the Royal Society Interface | *Molecular Systems Biology | *Cell Chemical Biology | *Cell | EMBO Reports | eLife | FEMS Yeast Research | Scientific Reports | Nature Methods | *Molecular Cell | Metabolic Engineering | Nature Microbiology | PLOS Biology | Cell Reports | The New England Journal of Medicine | Current Opinion in Biotechnology | Current Opinion in Chemical Biology | Nature Chemistry | Nature Biomedical Engineering | Plant Biotechnology Journal | bioRxiv | Trends in Biotechnology | *Nature Journals (Synthetic Biology) | Nature Journals (Biotechnology) | Nature Journals (Computational Biology and Bioinformatics) | Nature Journals (Neuroscience) | Nature Methods | Bioinformatics | arXiv | Cell Systems | Nature Aging | Neuron | Nature Neuroscience | Science Translational Medicine | BMC Biotechnology | Communications Biology | Nature Metabolism | Journal of Industrial Microbiology and Biotechnology | GEN Biotechnology | Npj Systems Biology and Applications | Nature Cell Biology | Gene | PNAS | Nature Reviews Microbiology | Journal of the American Chemical Society | Molecular Therapy | *Nature Plants | Molecular Plant | Plant Cell | Nature Machine Intelligence
📰 News & PR Websites
* = recommended.
*STAT | *WIRED News | *Science | Ars Technica | *Nature Biotechnology | *SynBioBeta | Tech Crunch | PR Newswire (Synthetic Biology) | PR Newswire (Biotechnology) | Proto.Life | The Guardian | GEN Eng News | Labiotech | NY Times | Fierce Biotech | Nature News | The Scientist | New Scientist | MIT Technology Review | Washington Post | Quanta Magazine | Timmerman Report | Genome Web | BiopharmaDive | Endpoints News
🏘️ Communities
* = Broad, open membership.
iGEM | Engineering Biology Research Consortium | ValleyDAO | Build-A-Cell | *DNA Deviants | *Bits in Bio | SBOL Community | Biodesign Challenge
Thanks for reading. Please send suggestions for improvements to my email.
— Niko McCarty
Love the list Niko, I remember putting together something similar in 2014 when I was learning what Synthetic Biology was - but this is far more comprehensive.
The only addition off the top of my head is in the biocontainment area, where I think you need a piece on engineered kill switches. Finn Stirling's work is the one that jumps to mind; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812007/
I'm a little bit surprised you don't have a protein engineering section, but that's a whole field.
Cheers!
Thank you so much Niko!