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From exploring cancer and virus targets to discovering active peptides through mRNA display
José Brango-Vanegas1, Michel Lopes Leite2, Kamila Botelho Sampaio de Oliveira1
1Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil; S-inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
Abstract:
During carcinogenesis, neoplastic cells accumulate mutations in genes important for cellular homeostasis, producing defective proteins. Viral infections occur when viral capsid proteins bind to the host cell receptor, allowing the virus to enter the cells. In both cases, proteins play important roles in cancer development and viral infection, so these targets can be exploited to develop alternative treatments. mRNA display technology is a very powerful tool for the development of peptides capable of acting on specific targets in neoplastic cells or on viral capsid proteins. mRNA display technology allows the selection and evolution of peptides with desired functional properties from libraries of many nucleic acid variants. Among other advantages of this technology, the use of flexizymes allows the production of peptides with unnatural amino acid residues, which can enhance the activity of these molecules. From target immobilization, peptides with greater specificity for the targets of interest are generated during the selection rounds. Herein, we will explore the use of mRNA display technology for the development of active peptides after successive rounds of selection, using proteins present in neoplastic cells and viral particles as targets.
Insights
mRNA display technology enables the development of targeted peptide therapies for cancer and viral infections by evolving peptides against specific proteins. This method allows for enhanced peptide activity using unnatural amino acids.
Area of Science:
- Biotechnology and Molecular Medicine
- Drug Discovery and Development
- Oncology and Virology
Background:
- Cancer and viral infections involve critical protein targets, presenting opportunities for therapeutic intervention.
- Defective proteins in neoplastic cells and viral capsid proteins are key players in disease pathogenesis.
Purpose of the Study:
- To explore the application of mRNA display technology for developing targeted peptide therapeutics.
- To generate peptides that specifically act on proteins in neoplastic cells and viral particles.
Main Methods:
- Utilizing mRNA display technology to select and evolve peptides from large nucleic acid libraries.
- Employing flexizymes for the incorporation of unnatural amino acids to enhance peptide activity.
- Implementing target immobilization and successive selection rounds to achieve high peptide specificity.
Main Results:
- Demonstrated the capability of mRNA display to generate functional peptides against selected protein targets.
- Showcased the potential for creating peptides with improved specificity and enhanced activity through unnatural amino acid incorporation.
Conclusions:
- mRNA display technology is a powerful platform for developing novel peptide-based treatments for cancer and viral diseases.
- The technology facilitates the evolution of highly specific and potent peptides by leveraging unnatural amino acids and iterative selection.
