Isaac Larkin

Since synthetic biology aims to redesign or build biological entities using biological parts, mapping how those parts fit together in natural living systems can serve as a guide for how to put parts together to attain a desired function. Mapping and reading genomes has lead to writing synthetic genomes that function in bacteria. Systems biology is involved in creating maps of biological interactions involving cells, genes, proteins and metabolic pathways in healthy and diseased living systems which can serve as a reference point for synthetic biology. At a meta level, mapping how different areas of synthetic biology and biological engineering are developing and could evolve in the future can help to identify promising areas for research

'Omics' Projects and Biological Atlases

Technical Roadmaps

• Engineering Biology Research Consortium (EBRC) Roadmap

• Addgene

The EBRC Roadmap is an attempt by members of the Engineering Biology Research Consortium (EBRC) to lay out the challenges and opportunities facing the development of synthetic biology and other biological engineering technologies from 2020 to 2040. Divided into four technical sectors (Engineering DNA, Biomolecule Engineering, Host Engineering, and Data Science) and five application sectors (Industrial Biotechnology, Health and Medicine, Food and Agriculture, Environmental Biotechnology, and Energy), the EBRC roadmap summarizes the current state-of-the-art for different areas of biological engineering, lists technical obstacles that must be overcome, and sets estimates/goals for what the near-term (2-5 years) and long-term (10-20 year) capabilities of the technologies should be.

DNA synthesis is the linking together of nucleotide bases such as the four naturally occurring ones, Adenine, Thymine, Cytosine and Guanine, to form a DNA molecule. During DNA synthesis non-natural nucleotide bases may also be incorporated into DNA.

Oxford Nanopore Technologies (also known as Oxford Nanopore) is a British biotechnology company that produces machines and kits for nanopore sequencing of both DNA and RNA. Oxford Nanopore's sequencing technology is based on measuring the voltage across a lipid membrane as a motor protein threads a single strand of nucleic acid through a transmembrane protein pore. This approach to reading DNA enables Oxford Nanopore to build small, low-power, inexpensive DNA sequencers; to sequence extremely long strands of DNA; and to perform rapid DNA sequence detection and analysis. These characteristics have lead to the use of Oxford Nanopore devices to perform genetic analysis in remote or extreme environments, such as deep in a rainforest or on the International Space Station; and to their use for rapid detection, diagnosis and analysis of pathogens in the field, such as during the 2014-15 Ebola outbreak in West Africa.

• iGemiGEM
• Open Foundry
• OpenFoundry
• BionetBionet project
• Open Bioeconomy Lab

• BIOMOD

Oxford Nanopore Technologies is a British biotechnology company that produces machines and kits for nanopore sequencing of both DNA sequencingand RNA. Oxford Nanopore's sequencing technology is based on measuring the voltage across a lipid membrane as a motor protein threads a single strand of nucleic acid through a transmembrane protein pore. This approach to reading DNA enables Oxford Nanopore to build small, low-power, inexpensive DNA sequencers; to sequence extremely long strands of DNA; and to perform rapid DNA sequence detection and analysis. These characteristics have lead to the use of Oxford Nanopore devices to perform genetic analysis in remote or extreme environments, such as deep in a rainforest or on the International Space Station; and to their use for rapid detection, diagnosis and analysis of pathogens in the field, such as during the 2014-15 Ebola outbreak in West Africa.

Oxford Nanopore Technologies is a British biotechnology company that produces machines and kits for nanopore DNA sequencing. The stated goal of the company Oxford Nanopore's sequencing technology is based on measuring the voltage across a lipid membrane as a motor protein threads a single strand of nucleic acid through a transmembrane protein pore. This approach to reading DNA enables Oxford Nanopore to build small, low-power, inexpensive DNA sequencers; to sequence extremely long strands of DNA; and to perform rapid DNA sequence detection and analysis. These characteristics have lead to the use of Oxford Nanopore devices to perform genetic analysis in remote or extreme environments, such as deep in a rainforest or on the International Space Station; and to their use for rapid detection, diagnosis and analysis of pathogens in the field, such as during the 2014-15 Ebola outbreak in West Africa.

Oxford Nanopore Technologies is a British biotechnology company that produces machines and kits for nanopore DNA sequencing. The stated goal of the company Oxford Nanopore's sequencing technology is based on measuring the voltage across a lipid membrane as a motor protein threads a single strand of nucleic acid through a transmembrane protein pore. This approach to reading DNA enables Oxford Nanopore to build small, low-power, inexpensive DNA sequencers; to sequence extremely long strands of DNA; and to perform rapid DNA sequence detection and analysis. These characteristics have lead to the use of Oxford Nanopore devices to perform genetic analysis in remote or extreme environments, such as deep in a rainforest or on the International Space Station; and to their use for rapid detection, diagnosis and analysis of pathogens in the field, such as during the 2014-15 Ebola outbreak in West Africa.

While the basecalling accuracy of Oxford Nanopore sequencers remains lower than those achievable by Sanger or Illumina sequencing, both per-read and consensus assembly accuracy have rapidly improved in the past few years.

On June 10 2015, Twist Bioscience closed a $37,000,000 series C funding round. Investors include: Foresite Capital, ARCH Venture Partners, Paladin Capital Group, Venture Investors, Fidelity Management & Research, IlluminaIllumina, Joby Pritzker, and Yuri Milner.

In April 2017, a Synthace announced a partnership with Cambridge AnalyticaConsultants. The partnership is focused on promoting the adoption and improvement of Synthace's Antha software. Cambridge AnalyticaConsultants is offering a consulting service to help companies get the most out of Antha by helping implement features of Antha in their labs such as; process development, protocol development, custom equipment development, and automation integration. The partnership is focused on promoting the adoption and improvement of Synthace's Antha software. Cambridge AnalyticaConsultants is offering a consulting service to help companies get the most out of Antha by helping implement features of Antha in their labs such as; process development, protocol development, custom equipment development, and automation integration.

Antha is an open source language and cloud based operating platform made by Synthace. Antha is made to help scientists design, execute, analyze, and replicate aspects of their lab work. The company claims that Antha can produce a 100X100-fold improvement in lab productivity, a %50% reduction in the time it takes to generate internal vector constructions, reducea lab33% costsreduction in the cost of running experiments by %33, and increase enzymatic activity by 100X compared to pre-Antha platforms. Below you can find brief descriptions of specific services Antha software offers to users which are: construct assembly, data integration, and liquid handling.

The CRISPR response evolved to defend bacteria and archaea against infection with bacteriophages , and CRISPR genes are present in the majority of bacterial and archaeal genomes. CRISPR systems share several common features: first, a mechanism for recognition and processing of foreign nucleic acids into short 'spacer' sequences; second, a mechanism for incorporation of these spacers into clusters (CRISPRs) on the bacterial genome, which are regularly interspersed by a short, repeated palindromic DNA sequence; third, a mechanism for transcribing and processing this CRISPR sequence into RNA molecules (known as CRISPR RNAs, or crRNAs) comprising the spacer sequence and a hairpin formed by the palindromic repeat; and finally, recognition and cleavage of DNA or RNA matching the spacer sequence by a protein-RNA complex consisting of both the crRNA and a nuclease. To avoid self-cleavage of the CRISPR locus in the microbe's genome, spacer sequences must occur next to a short DNA sequence, called the Protospacer-Adjacent Motif (PAM), which is not present in the CRISPR locus of the genome. This PAM sequence must be present in order for a spacer to be incorporated into the CRISPR locus, and must be present next to DNA/RNA matching the spacer in order for the crRNA/nuclease complex to recognize and cleave it. The genes and proteins involved with spacer acquisition, crRNA processing, and crRNA-guided cleavage are named CRISPR-Associated (Cas). In type II CRISPR systems, a single gene called Cas9 produces a DNA endonuclease which binds to the crRNA (which, when fused with a trans-activating crRNA, is called a short guide RNA or sgRNA), and can bind and introduce DNA double strand breaks at sequences matching the crRNA's spacer region. The Cas9/sgRNA complex can be programmed to cleave any PAM-adjacent DNA sequence, simply by changing the the spacer (also known as the guide) sequence. Cas nucleases from type V CRISPR systems (such as Cpf1/Cas12A) have also been adapted to programmably cleave DNA, while nucleases from type VI CRISPR systems (such as C2c2/Cas13A) have been adapted to programmably cleave RNA.

Clustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive immune response that provides immunity against foreign nucleic acids, such asparticularly viral DNA and bacterialor plasmidsRNA, through the use of crRNAs (CRISPR RNAs) and associated Cas genes.

The CRISPR response evolved within Bacteria and Archaea as a defense against attacks by one of the most abundant life forms on the planet — bacteriophages , and are present in the majority of Bacterial and Archaeal genomes. Several defense responses evolved over time as a defense to attacks from bacteriophages such as blocking absorption of bacteriophage DNA, prevention of bacteriophage DNA injection, restriction of foreign DNA, and abortive strategies. The CRISPR and cas system works with DNA repair and recombination genes as a part of an abortive strategy; where CRISPR is responsible for targeting specific foreign DNA elements and cas genes/enzymes are responsible for providing resistance and adaptive responses to those targeted elements.

The CRISPR response evolved to defend bacteria and archaea against infection with bacteriophages , and CRISPR genes are present in the majority of bacterial and archaeal genomes. CRISPR systems share several common features: first, a mechanism for recognition and processing of foreign nucleic acids into short 'spacer' sequences; second, a mechanism for incorporation of these spacers into clusters (CRISPRs) on the bacterial genome, which are regularly interspersed by a short, repeated palindromic DNA sequence; third, a mechanism for transcribing and processing this CRISPR sequence into RNA molecules (known as CRISPR RNAs, or crRNAs) comprising the spacer sequence and a hairpin formed by the palindromic repeat; and finally, recognition and cleavage of DNA or RNA matching the spacer sequence by a protein-RNA complex consisting of both the crRNA and a nuclease. To avoid self-cleavage of the CRISPR locus in the microbe's genome, spacer sequences must occur next to a short DNA sequence, called the Protospacer-Adjacent Motif (PAM), which is not present in the CRISPR locus of the genome. This PAM sequence must be present in order for a spacer to be incorporated into the CRISPR locus, and must be present next to DNA/RNA matching the spacer in order for the crRNA/nuclease complex to recognize and cleave it. The genes and proteins involved with spacer acquisition, crRNA processing, and crRNA-guided cleavage are named CRISPR-Associated (Cas). In type II CRISPR systems, a single gene called Cas9 produces a DNA endonuclease which binds to the crRNA (which, when fused with a trans-activating crRNA, is called a short guide RNA or sgRNA), and can bind and introduce DNA double strand breaks at sequences matching the crRNA's spacer region. The Cas9/sgRNA complex can be programmed to cleave any PAM-adjacent DNA sequence, simply by changing the the spacer (also known as the guide) sequence. Cas nucleases from type V CRISPR systems (such as Cpf1/Cas12A) have also been adapted to programmably cleave DNA, while nucleases from type VI CRISPR systems (such as C2c2/Cas13A) have been adapted to programmably cleave RNA.

CRISPR has been rapidly adopted in biotechnology research as it offers rapid genetic editing at a fraction of the time and cost of previous approaches. Whereas previous gene-editing approaches required protein engineering for each edit, CRISPR can be re-directed to a new site in the genome through supply of a new gRNA (guide RNA) complementary to the site of interest. While the first CRISPR variants based around native Cas9 suffered from high off-target mutagenesis rates, protein engineering and the discovery of additional CRISPR variations in bacterial species has led to a rapid proliferation of Cas9-related endonucleases, each with their own benefits and trade-offs. This family of tools is generally referred to as CRISPR. It comprises CRISPR-A/I acting as artificial transcription factors, high-fidelity CRISPR editing tools, drug-inducible endonucleases, and molecular imaging tools for DNA binding interactions. CRISPR systems are undergoing rapid development worldwide with application to diverse areas such as therapeutics, research tools, and ecological engineering. These developments have highlighted the potential safety issues inherent in a powerful genome editing technology, including their potential misuse and remediation thereof. Regulatory bodies have yet to issue specific guidelines for the safe use of CRISPR in therapeutics or any other systems, although such regulation will eventually prove necessary.

CRISPR has been rapidly adopted in biotechnology research as it offers rapid genetic editing at a fraction of the time and cost of previous approaches. Whereas previous gene-editing approaches required protein engineering for each edit, CRISPR can be re-directed to a new site in the genome through supply of a new sgRNA/crRNA complementary to the site of interest. While the first CRISPR variants based around native Cas9 suffered from high off-target mutagenesis rates, protein engineering and the discovery of additional CRISPR variations in bacterial species has led to a rapid proliferation of Cas9-related endonucleases, each with their own benefits and trade-offs. This family of tools is generally referred to as CRISPR. It comprises CRISPRa/CRISPRi acting as artificial transcription factors to regulate gene expression, high-fidelity CRISPR editing tools, drug-inducible endonucleases, molecular imaging tools for DNA binding interactions, and highly sensitive and specific detectors of both DNA and RNA. CRISPR systems are undergoing rapid development worldwide with application to diverse areas such as therapeutics, research tools, and ecological engineering. These developments have highlighted the potential safety issues inherent in a powerful genome editing technology.

Twist Bioscience was founded in 2013, and made their own high-throughput semiconductor-based DNA synthesis technology. Their technology allows them to overcome many of the barriers faced by other companies trying to manufacture DNA in high volumes. Problems that are overcome by semi-conductor based DNA synthesis are: producing too many errors in the genetic code during the manufacturing process, inability to produce synthetic DNA in high volumes, and producing affordable high quality DNA strands. Twist claims to have successfully industrialized a cost effective, high fidelity, and high through-put DNA synthesis platform capable of synthesizing DNA in high volumes.

Their semiconductor-based DNA synthesis technology greatly improved DNA synthesis. The miniaturizationBy ofminiaturizing the DNA synthesis process madeonto possiblemicrofabricated throughsilicon semiconductorswells and channels, Twist Bioscience has allowed Twistbeen Bioscienceable to improve the throughput of DNA synthesis by a factor of 1000. Throughput is greatly increased because semiconductor based technology allows the chemical reactions necessary for DNA synthesis to be reducedscaled down by a factor of 1,000,000. Twist Bioscience is able to produce 9,600 genes on a single silicon chip using their technology; compared to 1 gene being produced on the same amount of space using traditional DNA synthesis technologies.

Next generation sequencing (NGS) verified gene clones with no type II S sequencerestriction restrictionssequences and custom vector onboarding with verification. There is currently a lower limit of 10+ genes (no upper limit ) to place an order that will be ready within 20 business days.

Using ​combinatorial libraries for focused mutagenesis offers more flexibility and better representation than degenerate approaches. There are no unwantedSpecific codons may be excluded, codon ratio can be controlled, and all libraries are NGS verified.

DNA is being developed as a storage servicesmedium arefor underdevelopmentdigital data. Twist Bioscience is working with Microsoft and the University of Washington to improve data storage using DNA, and have published research demonstrating high-fidelity storage and random-access retrieval of over 200 MB of data, including an OK-Go music video. StoringAs datathe intechnology matures, DNA offerscould offer a low energyhigh-density, longlow-energy, termlong-term and secure data storage solution. Twist Bioscience hasexplains their work on DNA data storage technology as explained in their white paper.

Oligo pools are made to be diverse collections of oligonucleotides toand can be used for applications such as creation of CRISPR sgRNA libraries and high-throughput reporter essays. Oligo pools are made to be highly uniform and accurate for maximal oligo representation and have an error rate of approximately 1:1000 nucleotides (nt). sgRNA libraries and high-throughput reporter essays. Oligo pools are made to be highly uniform and accurate for maximal oligo representation and have an error rate of approximately 1:1000 nucleotides (nt).

Site saturation libraries are precise and diverse when compared to traditional directed mutagenesis techniques. Each saturation library is verified using NGS technology. Site saturation libraries are precise and diverse when compared to traditional directed mutagenesis techniques. They come free from unwanted codons and can be made to have specific codon ratios.

On May 27th, 2014 twistTwist Bioscience received $5.1 million dollars in funding from the Defense Advanced Research projects Agency (DARPA). The contract was awarded to Twist Bioscience under DARPA's Living Foundries program.

On Feb 10 2014, 2014 twistTwist Bioscience received $9,100,000 in series A funding from Asset Management Ventures (AMV) .

On May 27, 2014, Twist Bioscience receivedcompleted a $26,000,000 after completing their series B funding round. Investors include: DARPA, ARCH Venture Partners, Paladin Capital Group, Yuri Milner, and some undisclosed investors, and some undisclosed investors.

On June 10, 2015, Twist Bioscience receivedclosed a $37,000,000 after completing their series C funding round. Investors include: Foresite Capital, ARCH Venture Partners, Paladin Capital Group, Venture Investors, Fidelity Management & Research, Illumnia, Joby Pritzker, and Yuri Milner, ARCH Venture Partners, Paladin Capital Group, Venture Investors, Fidelity Management & Research, IllumniaIllumina, Joby Pritzker, and Yuri Milner.

On March 27th, 2017, Twist Bioscience receivedclosed a $61,000,000 after completing their series D funding round. Investors include: Foresite Capital., ARCH Venture Partners, Paladin Capital Group, Fidelity Management & Research, Fidelity Management and Research Company, Illumina, Boris Nikolic, Cormorant Asset Management, WuXi Healthcare Ventures, Fidelity Management, Yuri Milner, MerieuxMérieux DeveloppementDéveloppement, ARCH Overage Fund, Foresite Capital Management, WuXi, Corporate Venture Fund, Nick Pritzker, and Joby Pritzker.

On June 14th, 2017, Twist Bioscience receivedclosed a $27,000,000 after completing their series E funding round. Investors include: Biomatics Capital, Reinet Fund S.C.A, F.I.S, NFT Investment Limited, KangMei Group, Bay City Capital, GF Xinde Life Science Investment Fund, 3W Partners Capital, and Ditch Plains Capital Management LP.

On April 3rd 2018, 2018 Twist Bioscience received $50,000,000 in funding from private investors.

In June, 2016, Twist Bioscience became partners with Desktop Genetics —, a company using AI to create CRISPR screens. The partnership focuses on developing and integrating DNA synthesis tools and to design to design research protocols that enhance gene editing research. Desktop geneticsGenetics works with their customers to predictdesign CRISPR sgRNA CRISPR libraries for a cell line before sending this information to Twist Bioscience for sgRNA library synthesis. This partnership claims to aimaims to reduce cost and improve efficiency of gene editing research.

In June 2017, the BioBricks foundation partnered up with Twist Bioscience on the Free Genes project, an initiative to create aan open-source library of 10,000 genes that form biological parts important for synthetic biology. Twist Bioscience will be providing all the DNA that will be used for the project, and BioBricks will assemble a library of useful genes using its team and drawing on support from the scientific community. EverythingAll genetic constructs created through this partnership iswill basedbe onmade afreely available to the public through the Open Material Transfer Agreement, thatwhich allows anyoneany recipient to have freeuse, accessmodify, tocombine, copy, and redistribute the genes (in compliance with applicable biosafety and intellectual property laws).

In July 2017, Quintara Bioscience and Twist Bioscience became business partners, announcing they will be working together to create qBlock Gene Fragment and qGene DNA cloning services. Twist Bioscience will combine their silicon DNA synthesis technology with Quintara Bioscience's sequencing and cloning technologies to deliver gene fragment and cloning services.

Twist Bioscience and Synbio Technologies became partners on July 11th, 2017. The partnership seeks to combine technologies being used at both companies, by offering DNA strands up to 70 kilobases in length. Twist Bioscience will synthesissynthesize DNA strands up to 3.2 kilobases in length before shipping them off to Synbio Technologies for completion. This partnership gives both companies more international presence,: Twist Bioscience in located in FranceSan Francisco, and Synbio Technologies is in China, andso by working together they areplan to be able to offer improved DNA strand products that enhance scientific research for the diagnosis and treatment of disease.

On April 6th, 2016 Twist Bioscience acquired the Israeli software company Genome Compiler for an undisclosed price. Twist plans to use Genome CompilersCompiler's software developers and technology will allow Twist Bioscience to build an an ecommercee-commerce platform that allows customers to create their own gene designs online before ordering;, and haveto aleverage their strong software development team for future projects.

In it'sits early years, the biotech company was supported primarily through governments grants. Working on a variety of projects with different government agencies, such as the national science foundation and Defense Advanced Research Projects Agency (DARPA), before gaining access to venture capital funding in the summer of 2014.

Ginkgo Bioworks had pre-money evaluation of $350 million before receiving $100 million in its series C funding round on June 8th, 2016. The funding came from a number of old and new investors including: Y Combinator, Viking Global Investors, Senator Investment Group, Baillie Gifford, and Allen & Company .

On December 14th, 2017 Ginkgo Bioworks completed its series D funding round. The comapnycompany had a pre-money valuation of $725 million and gained an additional $275 million dollars in venture capital. The $275 million came from Viking Global Investors, Y Combinators Continuity fund, Cascade Investment, and Bill Gates. Ginkgo Bioworks is using the series D funding to build a BioworksS3 at its headquarters in Boston and hire an additional employees.

On September 23rd, 2016 Ginkgo Bioworks announced they will be working with Archer Daniels Midland Company (ADM) to design organisms capable of producing cultured ingredients for use in agricultural processing and food ingredient industries . ADM hopes to help Ginkgo Bioworks create new organisms that reduce cost and increase the sustainability of their agricultural processing and food ingredient business. ADM plans on using Ginkgo Bioworks for solving problems faced by their customers through providing novel ingredient production and formulation processes.

On March 20th, 2018, the German company Bayer and its crop science division announced they will be starting a new company called Joyn Bio.

Ginkgo Bioworks announced on September 22, 2016 that they will being partnering up with Cargill to help them improve their bio-industrial fermentationsfermentation processes.

On October 19th, 2016 Ginkgo Bioworks became partners with Prospect Bio. Prospect Bio and Ginkgo Bioworks are working together to create a new biosensor that will improve the speed and lower the cost of organism prototyping for new strain development. The biosensor underdevelopmentunder development will make the process of organism screening (testing for a desired trait) process faster. Organism screening is one of the slowest processes of the design, build, test system Ginkgo Bioworks uses for organism development. Normally, each organism created by Ginkgo Bioworks has to be screened individually. A biosensor allows for the screening of many organisms at one time. Ginkgo Bioworks is hoping for a forty-fold decrease in the cost of screening and increase the speed of creating commercial ready organisms.

On January 20th, 2017 Ginkgo Bioworks announced that it had acquired Gen9 — a company specializing in DNA synthesis. Ginkgo Bioworks previously contracted Gen9 to deliver 300 million base pairs in 2017, making Ginkgo Bioworks Gen9's biggest customerscustomer beforeprior to the acquisition took place.

Ginkgo Bioworks CEO, Jason Kelly, said in relation toof acquiring Gen9 "Our mission is to make biology easier to engineer and through that to enable our customers to grow better products. Having Gen9’s synthesis and assembly technology available to our customers is a valuable addition to our foundries, allowing us to further speed up the process of organism design".