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Published on: August 25, 2021
Protein-Based Therapeutic Killing for Cancer Therapies
Naroa Serna1, Laura Sánchez-García1, Ugutz Unzueta2
1Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain; Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina, 08193 Cerdanyola del Vallès, Spain.
Abstract:
The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis.
Insights
Cytotoxic proteins from nature are engineered into potent drugs for targeted cell killing, offering an innovative alternative to traditional cancer therapies. These engineered proteins can be designed for specific cell targeting and self-assembly into nanoparticles for advanced oncotherapy.
Area of Science:
- Biotechnology
- Molecular Biology
- Oncology
Background:
- High-incidence human diseases often require therapeutic cell killing.
- Current cancer treatments primarily rely on systemic chemical drugs with potential side effects.
- There is a need for more precise and targeted therapeutic strategies.
Purpose of the Study:
- To explore the adaptation of naturally occurring cytotoxic proteins as precise therapeutic agents.
- To engineer these proteins for enhanced functionalities beyond intrinsic cytotoxicity.
- To evaluate their potential in cell-targeted oncotherapy and theranostics.
Main Methods:
- Identification and isolation of cytotoxic proteins from diverse natural sources (bacteria, animals, plants, humans).
- Engineering of these proteins using DNA recombination to incorporate additional functions.
- Development of constructs capable of specific cell-surface receptor binding, self-activation, and self-assembly into nanoparticulate materials.
Main Results:
- Successfully engineered cytotoxic proteins demonstrate potent therapeutic activities.
- Engineered constructs exhibit recruited functions including targeted cell binding and self-assembly.
- These novel agents show promise for application in cell-targeted oncotherapy and theranostics.
Conclusions:
- Engineered cytotoxic proteins represent a promising innovative alternative to conventional systemic cancer drugs.
- The ability to recruit diverse functions into single pharmacological entities enhances their therapeutic potential.
- These protein-based agents offer broad applicability in targeted cancer treatment and diagnosis (theranostics).
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