The CRISPR Patent Battle

For this month’s main presentation, Albert Xue gave a comprehensive and entertaining overview of the patent interference proceedings between UC Berkeley and the Broad Institute over the patents for using CRISPR to edit eukaryotic genomes. Watch below, and feel free to comment if you have additional insights/opinions about this patent battle.

SynBio Newsreel, January 2017

Happy new year, synbio community! And also happy first anniversary of this blog, approximately. Joe Muldoon gave an excellent summary of the newsreel at today’s meeting; watch below, and then continue to the full linkstorm!

Synbio community news

• The United Nations biodiversity conference rejects calls for a moratorium on gene drives.
• A man attempts gene therapy on himself, with plans to commercialize his technique. Anyone interested in self-electroporation?
• David Baker’s lab shows up in The Atlantic, for their recent, jaw-dropping prediction of the structures for 614 uncharacterized protein families.
• Twist Bioscience summarizes some of the most important developments in synbio from the past year.

Synbio profiles

• Ginkgo Bioworks co-founder Tom Knight appears in Forbes. Main takeaway: it’s never too late to go back to school and learn a new field.

Industry news

• Editas licenses CRISPR-Cpf1 exclusively from the Broad institute for therapeutic applications, and non-exclusively to Monsanto for agricultural applications. Meanwhile the Doudna-Charpentier CRISPR teams have pooled their resources, with Intellia, Caribou, CRISPR Therapeutics and ERS Genomics all signing a mutual patent sharing and protection agreement.
• Oh snap! Ginkgo Bioworks acquires Gen9. This insightful Boston Globe commentary explains that the acquisition happened in large part because Gen9 ran out of funding in the cutthroat DNA synthesis market. Meanwhile, it looks like Ginkgo is trying to become the first vertically integrated synbio company. What will this mean for Twist Bioscience, now that their largest customer has bought its own DNA synthesis company?

Books, Longreads, Podcasts

• Nick Lane’s The Vital Question, which tackles the origins of both life and eukaryotes, is excellent. Fun fact from the book: multicellularity has independently evolved over 30 times, but endosymbiosis between prokaryotes (the origin of eukaryotes) has only given rise to complex cells once, as far as we know.
• Clarkesworld Magazine’s podcast is just what any sci-fi fan could want—a new short story (~20-90 minutes), read into your ears, every week. Lots of synbio speculative fiction here; I particularly enjoyed a recent episode (text version here) about two friends who make counterfeit steaks in China using high-end cell culture.

And now onto the research articles!

The strains, they are a-changin’

• Zhang et al. report the first organism to stably integrate and replicate unnatural DNA base pairs into its genome. If they can get to transcription and translation, the genetic code may be massively expanded. Summary in The Guardian.

Biomolecule engineering

• Brödel et al. turn one transcription factor into several, using directed evolution to engineer orthogonal cI variants and construct multiple genetic circuits from it.
• Northwestern alert! Schwarz et al. from Leonard lab design modular, synthetic extracellular signal transduction proteins to program Jurkat T Cells to produce an immunostimulatory response (IL-2) to an immunosuppressive signal (VEGF).
• Qudrat and Truong construct synthetic transmembrane proteins from minimal component domains that traffic efficiently to the plasma membrane in mammalian cells.
• How do you build your genes so they’re less expensive for cells to express? Frumkin et al. investigate, and find slower translation, more stable mRNA, and small hydrophilic amino acids are all important.
• Portela et al. develop a library of synthetic core promoters of different strengths for yeast cells. However, expression from a promoter differs significantly even between different yeast species. Universal synbio parts are hard to come by!

Genetic circuits and Metabolic Engineering

• To increase bioplastic production, He et al. engineer a genetic circuit that turns on only when high density (measured by quorum sensing) and stationary phase are reached.
• Crocker et al. use TALE protein fused to activator and repressor domains to develop a fully synthetic transcriptional regulation system in fruit flies. They then use this platform to explore the function of the pioneer/transcriptional enhancer Zelda, and to determine the best genetic architecture for generating sharp boundaries at the intersection of two developmental signaling factor gradients.
• Maurer et al. compare lab yeast with industrial yeast using quantitative trait loci (QTL) mapping, figure out the alleles which matter most for the industrial yeast’s productivity, and use CRISPR to put those alleles into lab yeast. The result is a lab yeast strain which outperforms the original industrial strain!

Plant Synbio

• Researchers improve the efficiency of photosynthesis in C3 plants by increasing the speed with which the plant’s photoprotective mechanisms kick in during high light intensity, and turn off during low light intensity. Legume Laboratory has a detailed summary.

CRISPR/gene editing

• Anti-CRISPR proteins discovered by Rauche et al. inhibit spCas9 activity, and may facilitate biocontainment and reduce off-target effects of CRISPR applications. GenomeWeb has the summary.
• Two new, compact CRISPR systems, dubbed CasX and CasY, discovered in uncultured archaea by a team including Jennifer Doudna. Their biochemistry and potential for genome editing applications should follow shortly, so watch this space! GenomeWeb has the summary.
• This is genetics on CRISPR. Peters et al. use an inducible CRISPRi library to produce a powerhouse study of essential gene knockdown and function in B. subtilis. One of those fun papers where the new results barely fit even in a Cell paper.

Computational biology

• Obertorner et al. from the Joint Genome Institute debut BOOST, a web design program for genetic parts that can modify sequences to make them easier/cheaper for for DNA synthesis companies to build.
• Gumulya and Gilliam present a really cool review of how sequence data from diverse evolutionary branches of life can be used to reconstruct approximate ‘ancestral’ enzymes, which are useful both for evolutionary biology and as starting points for protein engineering studies.

Engineering mammals

• Xie et al. efficiently treat diabetes in mice, using a capsule of human cells programmed to measure high glucose levels and release insulin in response. Classic Fussenegger lab work.
• YACs into HACs! Brown et al. develop an efficient method for transferring artificial chromosomes from yeast into human cell lines.
• Müller et al. reprogram mammalian fragrance receptors to generate a multi-cell analog-digital converter which can sense and perform digital logic operations in response to multiple odor molecules. Another powerhouse Fussenegger lab project.

Cyanobacteria: the Green E. coli

The November meeting’s main event was a presentation and discussion led by Quentin Dudley about the merits of photosynthetic cyanobacteria as a platform for synthetic biology applications. Watch the video below!

SynBio Newsreel, November

Hey look, we figured out how to embed video! Now you can watch a newsreel summary first, and then read any of the papers that sounded particularly interesting. There are fewer links this month because work in November+December was crazy, but rest assured the January newsreel will be just as exhaustive as usual!

Synbio community news

• Who needs CRISPR gene drives when you have Wolbachia? Scientists have successfully engineered the microbe, which lives in insect cells and spreads to all female offspring (while killing males), to render mosquitos inhospitable to dengue virus.
• The GP-Write white paper came out. STAT summarized it.
• iGEM happened! Many cool things. Grand prize winner was Imperial College London’s team, which engineered different strains of E. coli to co-culture at different population ratios.
• This year’s iGEM saw the launch of bionet, a P2P sharing platform for biological materials developed through the Biobricks foundation and a Drew Endy-led team.
• The Wyss Institute’s work on replacing animal drug testing models with human organoids on chips gets a write-up in Wired.
• UK researchers apply to perform field trials on wheat that has been modified to photosynthesize more efficiently, boosting yields 20% (in a greenhouse).

Industry news

• The Guardian profiles BioAmber and Bolt Threads, two companies trying to develop yeast-based pipelines for succinic acid and spider silk fabrics, respectively.
• PacBio sues Oxford Nanopore for infringing patents related to reading a single DNA molecule twice. OmicsOmics argues this lawsuit probably won’t damage Oxford Nanopore’s business, and is more an act of desperation from PacBio.

Now, on to the research papers!

Biomolecule engineering

• Younger et al. (from Leonard Lab!) builds and characterizes modular, ligand-responsive transcription repressors out of zinc finger proteins and small molecule binding domains.
• Control of gene expression with light continues to develop apace. Han et al. develop split T7 RNA polymerases which are activated by blue light.

CRISPR/gene editing

• Directed evolution may soon get easier. Researchers use dCas9 to recruit nucleotide deaminase proteins and induce hypermutagenesis at specific genomic sites.