Developing therapeutic proteins by engineering ligand-receptor interactions
Douglas S Jones1, Adam P Silverman, Jennifer R Cochran
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Abstract:
Ligand-receptor interactions govern myriad cell signaling pathways that regulate homeostasis and ensure that cells respond properly to stimuli. Growth factors, cytokines and other regulatory elements use these interactions to mediate cell responses, including proliferation, migration, angiogenesis, immune responses and cell death. Proteins that inhibit these processes have potential as therapeutics for cancer and autoimmune disorders, whereas proteins that stimulate these processes offer promise in regenerative medicine. Although much of the focus in this area over the past decade has been on monoclonal antibodies, recently there has been increased interest in the use of non-antibody proteins as therapeutic agents. Here, we review recent advances and accomplishments in the use of rational and combinatorial protein engineering approaches to developing ligands and receptors as agonists and antagonists against clinically important targets.
Insights
This review highlights advances in engineering non-antibody proteins, like ligands and receptors, for therapeutic applications. These protein therapeutics offer new strategies for treating cancer, autoimmune disorders, and for regenerative medicine.
Area of Science:
- Cellular biology and molecular medicine
- Protein engineering and drug discovery
Background:
- Ligand-receptor interactions are crucial for cell signaling, regulating homeostasis and responses to stimuli.
- These interactions mediate vital cellular processes such as proliferation, migration, angiogenesis, immune responses, and cell death.
- Therapeutic potential exists for both inhibitors (cancer, autoimmune disorders) and stimulators (regenerative medicine) of these pathways.
Purpose of the Study:
- To review recent progress in developing non-antibody protein therapeutics.
- To explore rational and combinatorial protein engineering approaches for creating novel ligands and receptors.
- To discuss the application of these engineered proteins as agonists and antagonists against clinically relevant targets.
Main Methods:
- Review of scientific literature on protein engineering techniques.
- Analysis of advancements in rational design and combinatorial approaches for protein therapeutics.
- Examination of case studies involving engineered ligands and receptors.
Main Results:
- Significant progress has been made in engineering non-antibody proteins for therapeutic use.
- Rational and combinatorial protein engineering enable precise modulation of ligand-receptor interactions.
- Engineered proteins show promise as agonists and antagonists for various clinical targets.
Conclusions:
- Non-antibody proteins represent a growing area of therapeutic development, complementing monoclonal antibodies.
- Protein engineering offers powerful tools to create targeted therapies for complex diseases.
- Further research in this field holds potential for innovative treatments in oncology, immunology, and regenerative medicine.
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