Implementation

Project Implementation

iGEM is Bringing Synthetic Biology to Reality

This section explains how we will implement our SkinBAIT project in the real world.

Product introduction

Our scabies treatment lotion offers an innovative approach to managing and preventing scabies infestations, and while more research and time are needed to make it applicable in real life, our team prefers to view our approach as a map of the journey from where we are today to the future that could be reached.

By harnessing genetically modified Cutibacterium acnes bacteria, the lotion produces Cry3Aa and Cry4Ba toxins, which specifically target and eliminate scabies. The formulation leverages the natural presence of C. acnes on the skin, ensuring effective integration and action. Easy to apply and designed for both treatment and prevention, our lotion provides a modern solution to scabies, addressing infestations with precision and care.

Target audience and scenarios

The first step in order to implement our product to the market is to define the possible interested customers. Our scabies treatment lotion is designed for individuals experiencing scabies infestations, including those suffering from intense itching and skin irritation caused by Sarcoptes scabiei mites. It is suitable for use across a broad range of demographics, including:

  • Individuals: for individuals with diagnosed scabies the lotion can be prescribed. It is formulated to be gentle on the skin while providing powerful mite-targeting action, promoting faster recovery and reducing discomfort, regardless of the age of the patient.
  • Providers: dermatologists, general practitioners, and other healthcare professionals can recommend and prescribe this innovative treatment to patients with scabies, offering a modern alternative to traditional insecticidal therapies, as they may cause adverse side effects, they are not suitable for preventive use and there are groups in the population for whom it is not recommended. Following initial treatment, the lotion can also then be used periodically to maintain mite-free skin and prevent recurrence, ensuring long-term protection and wellness.
  • Care facilities and high-risk communities: Institutions such as nursing homes, assisted living facilities, shelters or schools can utilize our lotion to manage and prevent scabies outbreaks among residents, aiding in the containment of the infestation and safeguarding the health of large groups.
  • Pharmaceutical companies and distributors: These entities play a vital role in the supply chain, ensuring that effective healthcare products reach pharmacies, hospitals, and clinics worldwide. By partnering with pharmaceutical companies, we can leverage their expertise in drug formulation, regulatory compliance, and market access. Distributors, on the other hand, have established networks that can help in the efficient and widespread distribution of your product. Focusing on these targets can enhance the reach and availability of our scabies prevention cream, ensuring it is accessible to a broad audience in need of effective preventive measures.
  • Veterinary Clinics: Veterinary clinics are another important target, as developing a lotion for pets could be a promising approach. These clinics could play a key role in recommending the product to pet owners, integrating it into a comprehensive strategy for managing and preventing scabies in animals. Pet owners, in turn, are highly motivated to keep their pets healthy and free from parasites. Offering a dual-use prevention cream can provide peace of mind and a convenient solution for households with pets, this could be useful since the presence of C. acnes has been detected on some dogs, cats and some rodents making compatible a similar approach for some pets and humans. This approach not only helps in preventing the spread of scabies but also promotes better overall health and hygiene within the home, fostering a safer environment for both pets and their human companions.

SWOT: Analysis for Genetically Modified Cream Targeting Sarcoptes scabiei

After a brief analysis of the possible market segments that we may interest, the second step would be to analyze the product that we are developing. This is achieved by doing a SWOT analysis, which allows us to define the strengths, weaknesses, opportunities, and threats of our product.

STRENGTHS:

  1. Innovative Approach: The use of genetically modified Cutibacterium acnes to target Sarcoptes scabiei is a novel method that sets your product apart from traditional treatments.
  2. Specific Targeting: The cream selectively targets the scabies mite without affecting human cells, which could reduce the risk of side effects and increase safety.
  3. Biocompatibility: Utilizing Cutibacterium acnes, a bacteria naturally present on human skin, may enhance the biocompatibility of the cream.

WEAKNESSES:

  1. Regulatory Hurdles: The introduction of Genetically Modified Organisms (GMOs) in a medical product might face stringent regulatory scrutiny, leading to potential delays and additional costs.
  2. Public Perception: There may be public resistance or skepticism towards the use of GMOs, particularly in healthcare products, which could hinder market acceptance.
  3. Development Costs: The research, development, and testing of such a unique product could require significant investment, increasing financial risk.
  4. Limited Knowledge Base: Since this is a novel approach, there may be limited existing research to guide product development, leading to potential scientific and technical challenges.

OPPORTUNITIES:

  1. Market Demand: There is a significant global market for effective scabies treatments, especially in regions where the condition is prevalent and current treatments are less effective.
  2. Partnerships and Collaborations: Opportunities exist to collaborate with biotech firms, academic institutions, and healthcare organizations to support research and development, as well as regulatory approvals.
  3. Expansion to Other Applications: The technology used in developing this cream could be adapted for other skin conditions or parasites, broadening the potential market.
  4. Rising Awareness of Scabies: Increased global awareness and efforts to combat scabies provide a conducive environment for introducing innovative treatments.

THREATS:

  1. Regulatory Barriers: Regulatory agencies may impose strict guidelines and lengthy approval processes for genetically modified products, potentially delaying market entry.
  2. Competition: There is always the risk of competitors developing alternative treatments that are more cost-effective or easier to market, particularly non-GMO based solutions.
  3. Intellectual Property Challenges: Protecting the intellectual property related to the genetic modification could be difficult, especially if competitors attempt to create similar products.
  4. Environmental Concerns: Potential concerns about the environmental impact of releasing genetically modified bacteria, even if harmless to humans, could attract negative attention and impact regulatory approval or public acceptance.

Market segmentation


Thanks to this segmentation analysis methodology extracted by the example proposed by the 2018 IGEM UPV Printeria Team we are now able to perform a more exhaustive analysis. This analysis would start by doing a plot that integrates all the information proposed on this table to analyze rapidly the results that we have obtained. You can interact with the plot to better understand our analysis!

CAME Analysis for Genetically Modified Cream Targeting Sarcoptes scabiei

MAINTAIN (STRENGTHS):
  1. Leverage Innovative Approach:
    • Continue to focus on the innovative nature of the product in marketing and communications, positioning it as a breakthrough in scabies treatment.
    • Maintain a strong research and development pipeline to keep innovating and potentially expanding the application of the technology.
  2. Highlight Specific Targeting:
    • Emphasize the product’s ability to specifically target Sarcoptes scabiei without affecting human cells, positioning it as a safer alternative to traditional treatments.
    • Incorporate this strength into branding efforts to differentiate the product in the marketplace.
  3. Capitalize on Reduced Resistance Risk:
    • Promote the product’s potential to reduce the risk of resistance development, making it a long-term solution for scabies treatment.
    • Work on gathering and publishing data to support claims of reduced resistance risk, adding credibility and appeal to the product.
  4. Emphasize Biocompatibility:
    • Highlight the biocompatibility of the product in marketing, emphasizing the use of naturally occurring bacteria on human skin.
    • Use this feature as a key selling point to attract customers looking for safer, more natural treatment options.
CORRECT (WEAKNESSES):
  1. Address Regulatory Hurdles:
    • Invest in regulatory expertise early in the development process to ensure compliance with all necessary guidelines. Collaborate with regulatory agencies to streamline the approval process.
    • Develop a comprehensive risk management plan to mitigate delays and additional costs associated with regulatory approvals.
  2. Improve Public Perception:
    • Launch educational campaigns to inform the public about the safety and benefits of GMOs in healthcare. Emphasize the safety and efficacy of the product in marketing materials.
    • Engage with key opinion leaders and healthcare professionals to advocate for the product, leveraging their influence to build trust.
  3. Manage Development Costs:
    • Secure funding through grants, partnerships, or investors with an interest in innovative healthcare solutions.
    • Implement cost-effective research and development strategies, such as outsourcing certain stages of the process or using open-source scientific data where applicable.
  4. Enhance Knowledge Base:
    • Collaborate with academic institutions and research organizations to build a strong scientific foundation for the product.
    • Invest in thorough preclinical and clinical studies to ensure a robust understanding of the product's efficacy and safety profile.
EXPLORE (OPPORTUNITIES):
  1. Expand Market Reach:
    • Explore opportunities in high-prevalence regions and underserved markets where effective scabies treatments are in demand.
    • Investigate the potential for expanding the product line to address other parasitic or skin conditions, using the same or similar technology.
  2. Forge Strategic Partnerships:
    • Seek collaborations with biotech companies, research institutions, and healthcare organizations to enhance product development, distribution, and market penetration.
    • Explore opportunities for joint ventures or licensing agreements to accelerate market entry and broaden reach.
  3. Leverage Rising Awareness:
    • Align product launches and marketing campaigns with global health initiatives aimed at combating scabies and other parasitic conditions.
    • Participate in awareness programs and health campaigns to position the product as a proactive solution in the fight against scabies.
  4. Broaden Technological Applications:
    • Explore the potential for the underlying genetic modification technology to be applied to other conditions, creating a platform for future products.
    • Invest in research to identify new targets for the technology, expanding its application beyond scabies.
ADAPT (THREATS):
  1. Prepare for Regulatory Barriers:
    • Build a flexible regulatory strategy that can adapt to different markets' requirements, allowing for smoother and faster approvals.
    • Engage in early discussions with regulatory bodies in target markets to anticipate and address potential challenges.
  2. Stay Ahead of Competition:
    • Continuously monitor the competitive landscape to anticipate and respond to emerging treatments. Focus on differentiating your product by highlighting its unique features, such as its specificity and reduced resistance risk.
    • Invest in ongoing research and development to improve the product and maintain a competitive edge.
  3. Strengthen Intellectual Property (IP):
    • Secure robust patents and trademarks to protect your intellectual property. Consider seeking international IP protection in key markets.
    • Regularly review and update your IP strategy to defend against potential infringements and to capitalize on new opportunities.
  4. Mitigate Environmental Concerns:
    • Conduct comprehensive environmental impact assessments to demonstrate the safety of releasing genetically modified bacteria.
    • Develop and communicate a clear environmental stewardship plan to address any concerns from regulators, stakeholders, or the public.

Future considerations

3-Domain Cry toxins kill insect larvae by disrupting their gut cells after ingestion. The toxins are activated by gut proteases and bind to cadherin receptors in the midgut. This binding leads to the formation of toxin oligomers, which insert into the gut cell membranes, forming pores that cause the cells to burst, leading to the larva's death.

In theory, disruption of any step of the toxin action pathway could cause insect resistance and has indeed led to resistance to Cry toxins evolving in different insects and nematodes. In general, the most frequently observed mechanism of Cry toxin resistance involves defects in receptor binding, followed by resistance owing to defects in protease production, elevated immune response, or enhanced esterase production.

Overcoming resistance to Cry toxins focuses on addressing the main mechanisms that larvae develop to avoid being killed by the toxins:

  • Modifying Cry toxins to bypass cadherin binding: Resistance often arises from mutations in the cadherin gene, preventing the toxin from binding. A solution is to modify Cry toxins by removing the helix α-1 region, allowing the toxin to oligomerize and form pores without needing cadherin binding. This method was successfully tested on resistant insect strains in Soberón et al. (2007)1, showing that modified toxins were effective against cadherin-deficient larvae.
  • Enhancing proteolytic activation: Cry toxins must be activated by proteases in the insect gut. Some insects may develop resistance by altering protease activity. An approach tested by Walter et al. (2008)2 introduced additional protease recognition sites in the Cry3Aa toxin, making it more easily activated in the insect gut. Applying this method to scabies larvae would require identifying the specific proteases in their gut and modifying the toxin to enhance its activation.

Both strategies, modifying the toxins to bypass receptor binding and improving activation through proteases, can help overcome insect resistance and restore the effectiveness of Cry toxins. Therefore, it would be interesting to deepen in the future in these areas in order to improve the overall treatment.

Bibliography

[1] Soberón M, Pardo-López L, López I, Gómez I, Tabashnik BE, Bravo A. Engineering modified Bt toxins to counter insect resistance. Science. 2007;318(5856):1640-2.
[2] Walters FS, Stacy CM, Lee MK, Palekar N, Chen JS. An engineered chymotrypsin/cathepsin G site in domain I renders Bacillus thuringiensis Cry3A active against Western corn rootworm larvae. Appl Environ Microbiol. 2008;74(2):367-74.