Team:UIUC Illinois/business-plan

The Company

Background and Location

Illinois Synth was formed directly as a result of the collaboration of members from the 2012 University of Illinois iGEM Team. The company corporate headquarters and principal product development facility will be located at the University of Illinois Urbana-Champaign’s Institute for Genomic Biology. Upon expansion and generation of a consistent revenue stream, Illinois Synth will look to occupy the Enterprise Works Tech Incubator located at 60 Hazelwood Drive, Champaign IL.

Facilities

Illinois Synth’s manufacturing and laboratory facilities and equipment are all serviced regularly to maintain the highest performance standards consistent with aseptic technique. Additional capital equipment is projected subsequent to product release to utilize capacity and meet sales demand.

Legal Form of Business

The company will be incorporated as a C-Corporation in the state of Delaware.

Employees

The management team of six executives will look to conduct research and development independent of other employees for the first three quarters of company growth. Future expansion in the fourth quarter and beyond will require several production and sales personnel.

Marketing Plan

Industry Profile

The global synthetic biology market is estimated to grow to $4.5 billion over the next three years. This is due to major developments in biomedicine, pharmaceutical drug synthesis, energy and environmental research, biomaterials, nanotechnology, and biosecurity. There have been significant investments in the industry by companies such as Amyris Inc, GeneScript, Bayer, and Blue Heron Biotechnologies. Additionally, developments in DNA synthesis and sequencing technologies and bioinformatics have catalyzed the progress of synthetic biology ever since the creation of the first synthetic cell in 2010. Synthetic biology is being recognized around the world as an emerging technology that has the potential to provide solutions to energy and food shortage, pollution, infectious diseases, and even climate change. The following diagram depicts the distribution of the global synthetic biology market share, as of 2011:

Competitive Analysis

Direct Competition

Competition for the GEM Toolkit product development line primarily takes the form of other types of RNA binding proteins shown below:

Competitors to IOPiC include alternative ways to produce piceatannol, which currently only take the form of chemical synthesis by companies such as Sigma-Aldrich, Santa Cruz Biotech, and Tocris Bioscience. A price comparison of the three companies is shown below:

Indirect Competition

Indirect competition to the field of synthetic biology as a whole is high, given other technologies that have been around for decades. In the specific niche market within which Illinois Synth is positioned, however, such competition is negligible, because of the inability of non-biological tools to regulate micro-scale biological processes such as gene expression.

Future Competition

Future competition will likely come in the form of new technologies and findings. Proteins with higher binding specificities with a great degree of customizability would render our GEM Toolkit obsolete. Additionally, chemical processes that produce piceatannol with a high efficiency at a low cost would cause a great reduction in the utility of IOPiC. Other compounds, if found to greatly inhibit adipogenesis, could also make a piceatannol-production system unnecessary. Based on current research results, Illinois Synth does not expect such developments to arise in the next decade, will continue to monitor all relevant research, and expects to exit the market prior to major technology advances.

Market Analysis

Target Market Profile

Illinois Synth expects that its products, particularly IOPiC, its piceatannol-production cascade will require a substantial amount of developmental effort. Government approval will likely be required to market any product that involves the use of bacterial cell culture to produce a compound that would be tested with human adipocytes. The company will take the necessary steps to patent and license its products in the United States, as well as negotiate with pharmaceutical companies abroad to obtain marketing approval in a particular country. The target market for Illinois Synth’s products, therefore, will take several forms, including:

• Academic Research Labs
• Industrial Research Labs
• Governmental Research Labs
• Pharmaceutical Competitors

Sales Channels

Our marketing team will make contact with academic universities institutions that are involved in Synthetic Biology research. This will likely be done by leveraging connections to members and advisors of iGEM teams at some of these academic institutions. We will provide our GEM Toolkit at no cost to these institutions, and will look instead to establish a reputation for the product. Upon receiving feedback about the GEM Toolkit, we will look to make any necessary changes or improvements before commercializing it.

Next, the company will look to enter into distribution agreements for the registration and sales of its products in the United States, and eventually foreign countries. These distribution agreements will take the form of contracts with research labs at biotechnology firms, as well as certified manufacturers of chemical compounds such as Sigma-Aldrich.

Illinois Synth will also actively pursue online advertising, advertise our products at biotechnology oriented trade shows, and release a monthly newsletter to keep potential and current customers updated about product developments.

Product Plan

Purpose of Products

Gene Expression Modulator (GEM) Toolkit

The GEM toolkit will be developed around the features of the Pumilio and FBF homology (otherwise known as PUF) protein domain of the human PUM1 gene. PUF proteins are found in most eukaryotes, and have the unique ability to be programmed to recognize any 8 nucleotide ssRNA sequence. Illinois Synth has successfully demonstrated that this PUF domain can be tethered to other functional domains, such as an endonuclease for the purpose of silencing gene expression through site specific mRNA cleavage. Our findings came in the form of biobricks that have a wide range of possible functions including gene expression modulation and the scaffolding of metabolic pathways.

In Vivo Optimized Piceatannol Cascade (IOPiC)

IOPiC is in essence an enzymatic conveyer belt, combining the functionality of the programmable PUF protein with a designer RNA scaffold, to achieve the low cost, and efficient production of the compound piceatannol, a compound that inhibits the process of adipogenesis, or fat-cell formation. The reason piceatannol was chosen as the compound of interest was due to a study conducted at the Kee-Hong Kim lab at Purdue University. The study demonstrated how piceatannol binds to the insulin receptors found on preadiopocytes, impairing the cells ability to control cell cycles and successfully develop into adipocytes. The following video provides an overview of the findings of the Kim laboratory, and the potential impact piceatannol may have in controlling obesity, one of the most of most widespread diseases of the 21st century.

Features and Benefits

Gem Toolkit

RNA has characteristics that are important in human gene expression (i.e. alternative splicing of mRNA, noncoding RNA). Therefore, a modular RNA binding protein is an invaluable tool for gene regulation. The PUF domain of human PUM1 gene contains eight tandem repeats, each recognizing one of the four nucleotide bases. In theory, a PUF protein can be programmed to recognize any 8-nt ssRNA sequence. Illinois Synth has demonstrated that PUF can be tethered with other functional domains for applications in E. Coli. Specifically, we have shown that a PUF/endonuclease fusion protein acts as RNA scissors, silencing gene expression through site specific mRNA cleavage. The GEM Toolkit of PUF biobricks will offer an extension of the abilities of PUF to regulate and control gene expression. A schematic of some of these functions is shown in Figure 1.

IOPiC

Obesity is today one of the leading preventable causes of death worldwide, and given the recent discovery of piceatannol’s anti fat cell properties, we foresee demand for efficient, low cost, piceatannol production by research labs, and eventually pharmaceutical companies to increase dramatically over the next decade. Illinois Synth has also tethered the PUF protein domain to split GFP to test its ability to co-localize proteins using a RNA scaffold. This proof of concept will be the basis for IOPiC, which will also take the form of an RNA Scaffold, and will catalyze the production of piceatannol from L-tyrosine along the pathway depicted in Figure 2.

The GEM toolkit will be used to tether PUF domains on the RNA scaffold to the TAL, 4CL-STS, and BM3 enzymes as shown in Figure 3.

Value Proposition

• Breakthrough technology in regulating ssRNA gene expression
• Cost efficient piceatannol production scaffold, superior to chemical synthesis
• Continuous research and product improvements
• Proof of concept demonstrated
• Supporting literature to direct product development

Proof of Concept

Tests conducted by our team of engineers have proven the ability of PUF to tether to an endonuclease functional domain to facilitate gene silencing. Additionally, studies by the Pamela Silver group at Harvard University have successfully demonstrated the utility of an RNA scaffold to catalyze H+ production. The programmable ability of PUF to target a specific 8-nt sequence is documented in a variety of literature studies, referenced under Attributions.

Stage of Development

Illinois Synth is currently in its early developmental stage of product development. While the proof of concepts for our products has been established, additional research is required to produce functioning prototypes of the GEM Toolkit and IOPiC. Once complete, we expect both products to follow the following life cycle:

Intellectual Property

Illinois Synth will have the policy of using patents, trademarks, and trade secrets to protect the results of its research and development activities and, to the extent it may be necessary or advisable, to exclude others from appropriating its proprietary technology. That being said, the company's policy is to advance the progressive of synthetic biology by making its products available at competitive prices, collaborating with universities and academic institutions to further research and development, and providing discounts and sponsorships to research groups that may benefit from our technologies.

Disclosure

Illinois Synth has stringent policies and procedures for ensuring that all intellectual property is protected prior to any public disclosure of new products or technologies.

Product/Service Liability

Governmental trials or marketing of Illinois Synth’s biological-microorganism-based products may expose the company to liability claims from the use of the products. Illinois Synth will therefore carry liability insurance for that purpose. Due to the maintenance of hazardous materials at its lab facilities, it is subject to federal, state, and local laws and regulations governing the use, manufacture, storage, handling, and disposal of hazardous materials and waste products. In the event of an accident, the company could be held liable for resulting damages. The company will therefore maintain a database of technical product related inquiries from all users of our product, academic and industrial. Illinois Synth will also maintain a record of all complaints or reports of an actual or potential failure of any product to meet the specifications set forth in regulatory filings.

Product/Service Support

Product information materials will be put in place explaining proper use and efficacy of direct sale merchandise. This will take the form of lab protocols, safety instructions, brochures, and contact information for any problems and complaints.