Collections/Drug Delivery Projects
iGEM 2013 Drug Delivery Projects
One of the tasks which microorganisms can do well is produce medically useful molecules. One of the first examples of such a case is using genetically engineered E. coli to produce insulin (called "Humulin") for diabetics. The company Genentech was founded to commercialize this venture and still exists today as a wholly owned subsidiary of Roche.
Here are examples of iGEM teams in 2013 which worked on drug delivery systems and other medically-useful systems.
Paris Bettencourt 2013: Fight Tuberculosis with Modern Weapons!
Health & Medicine Track
Winner, 2013 Overgraduate section
Abstract: We are testing new weapons for the global war against Mycobacterium tuberculosis (MTb), a pathogen that infects nearly 2 billion people. Our 4 synergistic projects aim to help in the prevention, diagnosis, and treatment of tuberculosis. 1) We are reproducing an essential MTb metabolic pathway in E. coli, where it can be easily and safely targeted in a drug screen. 2) We are building a phage-based biosensor to allow the rapid diagnosis specifically drug-resistant MTb strains. 3) We are constructing a mycobacteriophage to detect and counterselect drug-resistant Mtb in the environment. 4) We are programming E. coli to follow MTb into human macrophages and saturate it with bacteriolytic enzymes. We want to vanquish tuberculosis and build a TB-free world.
From the team's 2013 wiki: To defeat tuberculosis, we need new biotechnology. Our work adds 4 new tools to the anti-TB medical armamentarium. Detect - a CRISPR-based biosensor delivered by phage and sequence-specific for antibiotic resistance. Target - an E. coli model hosting an essential mycobacterial metabolic pathway that could simplify drug screening. Infiltrate - an E. coli strain capable of entering infected macrophages and lysing mycobacteria. Sabotage - a non-lytic phage that spreads horizontally in a bacterial population and expresses an siRNA to knock down antibiotic resistance.
EPF Lausanne: Taxi.Coli: smart drug delivery
New Application Track
Abstract: EPF Lausanne’s team is proud to participate to iGEM 2013 and excited to present their project: Taxi.Coli: smart drug delivery. The team’s vision is to build a biosynthetic drug delivery concept. The key word of this project is “adaptability”. Our goal is to explore a way of using E.Coli as a highly modular carrier, opening the gate to several applications and alternatives in disease treatments. Using the principles of synthetic biology, we engineered a gelatinase secreting E. Coli able to bind gelatin nanoparticles using a biotin-streptavidin interaction and release them in a corresponding location. The drug delivery system is built in three parts: 1) the nanoparticle binding and 2) the environment sensing that 3) triggers the gelatinase release of the engineered E. Coli, liberating the content of the nanoparticle. The nanoparticles made of gelatin are able to carry any type of organic compound leading to a wide range of applications.
Groningen: Engineering Bacillus subtilis to self-assemble into a biofilm that coats medical implants with spider silk.
Health & Medicine Track
Abstract: Approximately half of all implanted medical devices result in one or more medical complications, which have been found to increase mortality rates by 25%, and to cost the American society an additional 30 billion dollars every year. A possible solution for these complications is to form a protective biocompatible layer between the implant and the body by means of a spider silk coating. This is achieved through mathematical modeling, techniques from the synthetic biology, and the Gram-positive bacteria Bacillus subtilis, which is redesigned to secrete silk and to self-assemble into a biofilm surrounding the implant. It uses a modified chemotaxis system coupled to the DesK heat sensing system to do so. B. subtilis is furthermore often used in the industry for the commercial production of extracellular proteins, and is generally regarded as safe.
From their wiki: Bone fractures and other physical problems are often solved with implants. Unfortunately about half of the implants give rise to complications, such as inflammations, infections and rejection by the host. To reduce negative effects a protective and biocompatible coating can be applied to the implant, prior to insertion into the body. A very potent material to use for this coating is spider silk. Not only does it exert great biomedical properties, it also has high tensile strength, elasticity and is biodegradable.
The focus of this project is to coat an implant with recombinant spider silk. Bacillus subtilis cells were transformed to enable spider silk production, and to introduce a novel heat triggered system.
By addition of a signal sequence to the silk protein gene the bacterium is able to export the protein out of its cell. Also a Strep-tag® is added to the silk protein sequence. B. subtilis is inherently able to sense temperature, and by coupling this sensor to its movement system the cells will become immobilized near the implant. This trick allows efficient and localized production of spider silk near the heated implant, to which the Strep-tagged silk proteins can attach. After processing and thorough sterilization, which the spider silk coating can withstand, the coated implant is ready for use.
NJU China: Biomissile: a novel drug delivery system with microvesicle
Health & Medicine Track
Abstract: Recently, small interfering RNA (siRNA) has emerged as a promising therapeutic drug against a wide array of diseases. However, site-specific delivery has always been a challenge in gene therapy. Microvesicles (MVs) are lipid-bilayer vesicles which are naturally secreted by almost all cell types, playing crucial roles in intercellular transport of bioactive molecules. Given the intrinsic ability to naturally transport functional RNAs between cells, MVs potentially represent a novel and exciting drug carrier. In our project we are trying to express both anti-virus siRNA within the cell and target protein on the surface of the MVs by engineering the HEK 293T cell, which is capable of producing large amounts of MVs. Thus, the MVs produced by our engineered HEK 293T cells will contain the siRNA and be able to specifically deliver the siRNA to the sites we want, acting as biomissile for the targeted destruction of the disease.
Health & Medicine Track
Abstract: Gram negative bacteria produce outer membrane vesicles (OMV) in the size range of 20-200nm. Whereas their function and contents has been studied for decades, their potential as drug carriers has not been investigated before. We want to introduce protein G from Streptococcus dysgalactiae subsp. equisimilis into Escherichia coli OMV's. Protein G is known to bind to human serum albumin (HSA) which helps S. dysgalactiae subsp. equisimilis hide from the immune system. The second part of our project is to introduce fluorescent proteins (FP's) linked together into the vesicles. Introducing protein G and linked FP's into the vesicles will demonstrate that it is indeed possible to manipulate the content, and therefore the properties, of OMV's.
USTC China: T-VACCINE
New Application Track
Abstract: T-VACCINE is a vaccine initiating immune response by penetrating the skin with the aid of transdermal peptide. From now on, injections are simply history. Based on the theory of user-friendly, a special group of engineering bacteria which produce T-VACCINE is used to create a brand-new "band-aid" serving as a guardian of our health. We have found a kind of transdermal peptide TD-1,a magical molecule that enhances the permeability of the skin as well as draw filamentous bacteriophages into the skin. By combining the gene fragments of antigen,immune adjuvant LTB and Luman-recruiting factor TNLFα with that of the TD-1, our team got the permeable fusion protein. In order to obtain large amount of extracellular protein, we chose Bacillus subtilis WB800N as our expression chassis. Further more, the universality of our experimental method is verified by the adoption of various antigen of existing vaccine, such as HBsAg, PA and AG85B.
Virginia: Minicells: Multi-Purpose Nano Chassis
Foundational Advance Track
Abstract: Overexpression of the tubulin-homolog FtsZ leads to asymmetric cell division in E. coli that yields achromosomal "minicells." The lack of a chromosome renders minicells unable to replicate and cause infection, yet they still retain and express plasmid genes. Furthermore, minicells inherit the stable, non-leaky membranes and cytosolic composition from their parent cell. Our project design is centered on the creation of an IPTG-inducible FtsZ Biobrick that permits tunable overexpression for optimal minicell production. With the development of a multi-purpose, innocuous bacterial chassis as our ultimate goal, we incorporated three additional safety elements: the Ail protein, a polysialic acid capsule and de-acylated lipopolysaccharide. Both Ail and the PSA capsule serve to prevent complement deposition on the surface of the minicells, with PSA also protecting against antibody opsonization. Finally, LPS toxicity is reduced by inducing minicell formation in an lpxM mutant strain that lacks a critical myristoyl transferase for late-stage acyl modifications.