Salmonella-Based Drug Delivery System Development
InquiryCD Formulation has focused on advancing the next generation of microbial delivery platforms. By leveraging our deep expertise in molecular biology and microbial engineering, we have generated a versatile Salmonella-based drug delivery system. Our live-attenuated Salmonella strain vectors are precisely designed to incorporate a variety of drugs, proteins, nucleic acids and nanoparticles into our Salmonella delivery vehicles to invade target tissues and release therapeutic payloads intracellularly.
How Does Salmonella Apply to Drug Delivery?
Salmonella possesses properties making it a promising vehicle for drug delivery applications. As a native intestinal bacterium, it can colonize the gastrointestinal tract and penetrate epithelial cells. Genetic engineering allows Salmonella to be tailored for the targeted delivery of therapeutics such as proteins, nucleic acids, and nanoparticles directly inside cells. Attenuated strains maintain sufficient invasiveness while limiting pathogenesis. This drug delivery method can safely and effectively deliver drugs orally to treat gastrointestinal diseases and deliver vaccines or cancer treatments.
Tumor-targeted delivery of lnc antisense RNA using Salmonella (Sivasankar C.; et al. 2023)
How Do We Develop Salmonella Vectors for Nucleic Acid Delivery?
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Generation of Attenuated Strain
Knock out virulence genes to reduce pathogenicity.
Maintain ability to invade and survive inside host cells.
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Vector Construction
Design and engineering of Salmonella-based plasmids with appropriate genetic modifications.
Add antibiotic resistance genes and the origin of replication.
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Transformation and Culture
Transform the engineered vector into the appropriate host strain.
Culture transformed Salmonella strains under controlled conditions to promote vector replication and maintenance.
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Infection and Uptake
In vitro or in vivo infection of target cells or organisms with engineered Salmonella vectors.
Uptake of the Salmonella vectors by host cells, facilitated by their natural invasion and colonization abilities.
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Intracellular Trafficking
Utilization of Salmonella's innate intracellular trafficking mechanisms to transport the vectors into the desired cellular compartments.
Facilitation of the release and expression of the delivered nucleic acids within the host cells.
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Immunogenicity and Safety
Evaluation of the immunogenicity and safety profile of the Salmonella vectors to ensure minimal adverse effects.
Modification of the vectors to reduce immunogenicity and enhance safety.
Applications of Our Salmonella-Based Drug Delivery System
Our Salmonella-based system targets cancer cells, delivering therapeutic agents directly to tumors while minimizing harm to healthy tissues, making it a promising approach to targeted cancer therapy.
Leveraging Salmonella's unique properties, our engineered strains act as effective carriers for vaccines, enhancing immune responses and potentially reducing the number of vaccine doses required.
By incorporating therapeutic genes into the Salmonella vector, our platform enables targeted delivery of genetic material to specific cells, addressing genetic disorders and promoting desired therapeutic outcomes in gene therapy applications.
- Infectious Disease Treatment
Our Salmonella-based system demonstrates potential for treating infectious diseases. We engineer bacteria to produce antimicrobial agents or directly combat pathogens, bolstering the body's natural defenses against infections.
S. enterica as a delivery system for heterologous molecules in cancer therapy (Becerra-Báez E.I.; et al. 2022)
Advantages of Our Salmonella-Based Drug Delivery System
- Salmonella is able to invade and survive within host cells, releasing the payload within the target cellular compartment.
- Genetic modifications allow control over the bacteria's interaction with different cell and tissue types.
- The platform is compatible with a wide range of drugs, proteins, nucleic acids, nanoparticles and other agents.
- Attenuation techniques minimize pathogenicity while maintaining delivery properties.
CD Formulation possesses comprehensive capabilities from strain design and optimization through full characterization, and toxicology assessment. Our live-attenuated Salmonella vectors can be customized to preferentially accumulate and release cargo within select tumor or organ microenvironments. If you are seeking an innovative drug delivery solution, please contact us!
References
- Sivasankar C.; et al. Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice. Mol Ther Nucleic Acids. 2023, 34:102053.
- Becerra-Báez E.I.; et al. Recombinant attenuated salmonella enterica as a delivery system of heterologous molecules in cancer therapy. Cancers (Basel). 2022, 14(17):4224.
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