Contribution

    Contribution

  1. Introduction
  2. Chimeric Autoantibody Receptor
  3. HCR & CRISPR/dCAS9/VPR Part Collections
  4. Promoter-RBS Selection Software
  5. Fundraising Operations Framework

Introduction

Contribution stands as a core value of the iGEM competition, emphasizing collaboration, innovation, and the ethical foundation of research. This year, we are proud to introduce our novel concept of Chimeric AutoAntibody Receptors (CAAR), specifically designed for autoimmune diseases. Our contribution includes a modular receptor design workflow, complete with DNA and amino acid sequence databases, codon optimization tools, and structural modeling software. This provides a comprehensive guide for iGEM teams, empowering them to develop their own CAAR constructs tailored to various diseases. Moreover, our Promoter-RBS selection software offers a machine-learning-based tool to optimize gene expression, making CAAR design more scalable and efficient. We hope our efforts will inspire future teams, providing a foundation for expanding autoimmune disease therapies and synthetic biology innovations.

Receptor Parts Software Fundraising

Chimeric Autoantibody Receptor

Literature Findings

We are thrilled to demonstrate the concept of a Chimeric AutoAntibody Receptor (CAAR), a concept we are the first to present to the iGEM community. We go into depth about its operation in our Design Page and why it is the best substitute for CAR-T cell treatment, as well as how it can be specifically adjusted to treat autoimmune diseases.

CAAR Design Workflow

Additionally, we created and recorded a simplified process for creating a modular receptor that incorporates all of the structural modeling software, codon optimisation tools, and databases of DNA and amino acid sequences that we utilized. It is available in its own space of the Design Page and provides iGEMers with step-by-step guidance on how to design their own construct. Please utilize it and build upon it!

Modular CAAR Part Collection

We have submitted a CAAR part collection of 20 new basic parts in the iGEM registry. Some of them encode the four new composite CAARs we designed specifically for multiple sclerosis. Six parts (BBa_K5310000 and BBa_K5310007-BBa_K5310011) are standard receptor components that were selected due to their efficacy, safety and ability to enhance CAR-T cell survival and proliferation.

The 20 new basic parts can be used as building bricks to engineer a new CAAR or CAR that binds a different MS autoantibody or a different disease altogether. The construct is modular and therefore easily adaptable.

Two of the basic parts (BBa_K5310001 and BBa_K5310003) are the immunogenicity- inducing peptides of myelin proteins MOG and MBP. They can be integrated into the receptor or expressed individually for researching multiple sclerosis and other demyelinating autoimmune diseases such as myelin oligodendrocyte glycoprotein (MOG)-associated disease, or optic neuritis.

Future iGEM teams who choose to take on therapeutic initiatives against cancer or autoimmune disease will undoubtedly find our part collection interesting. We welcome any of them to make use of our efforts!

HCR & CRISPR/dCAS9/VPR Part Collections

We have curated two additional part collections to further expand the registry. Our HCR Collection contains seven new basic parts (BBa_K5310020-BBa_K5310026), designed to execute a chain of consecutive molecule hybridizations and releases. This process begins with the detection of two disease biomarkers selected from the transcriptome and ends with the release of two therapeutic molecules selected as putative therapeutic targets. Each part is documented to explain its role in the mechanism and can be used for replication and testing.

Our CRISPR Collection contains 10 new basic parts (BBa_K5310027-BBa_K5310036) which encode sgRNAs for CRISPR-dCAS9-VPR epigenetic induction of FOXP3.

Promoter-RBS Selection Software

We designed our project with the objective of creating a modular system for scalable production of CAARs from the very beginning. But deciding which combination of promoters and ribosome binding sites (RBS) is appropriate for their target sequence is a mystery to any young synthetic biologist due to the wide range of options available.

We made the decision to create two machine learning models that help users choose promoters and RBSs during the design process, drawing inspiration from the iGEM Tsinghua 2023 Software Tool.

Future iGEM Teams can now use our bioinformatics tool for any procedure that calls for careful consideration of expression factors, such as promoter strength! Furthermore, as our software can still be considerably improved in terms of functionality and model performance, future iGEM teams might think about expanding it further as a possible iGEM Software Tool Project.

Our code is available in our GitLab Repository, along with instructions for model training and deployment. Our Software Page contains more information about the development of our software tool. We welcome contributions from the community!

Fundraising Operations Framework

A crucial but often overlooked part of iGEM projects is securing the funding that makes everything else possible. To help teams plan their fundraising efforts, we put together a framework to categorize potential sponsors based on their connection to different aspects of the project and the resources they could provide. This categorisation helped us tailor our approach, since each group has different motivations for partnering with us. Furthermore, since financial transactions require careful handling, we documented our contact with sponsors to streamline the process.

We have also shared a downloadable template of our framework, in the hopes that it will assist future iGEM teams and make the stressful fundraising process more manageable. If the template of our framework does not render below, you can view it here.