Designing cytochrome P450 enzymes for use in cancer gene therapy

Carrera-Pacheco, Saskya E. and Mueller, Alexander and Puente-Pineda, Juan A. and Zúñiga-Miranda, Johana and Guamán, Linda P. (2024) Designing cytochrome P450 enzymes for use in cancer gene therapy. Frontiers in Bioengineering and Biotechnology, 12. ISSN 2296-4185

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Abstract

Cancer is a significant global socioeconomic burden, as millions of new cases and deaths occur annually. In 2020, almost 10 million cancer deaths were recorded worldwide. Advancements in cancer gene therapy have revolutionized the landscape of cancer treatment. An approach with promising potential for cancer gene therapy is introducing genes to cancer cells that encode for chemotherapy prodrug metabolizing enzymes, such as Cytochrome P450 (CYP) enzymes, which can contribute to the effective elimination of cancer cells. This can be achieved through gene-directed enzyme prodrug therapy (GDEPT). CYP enzymes can be genetically engineered to improve anticancer prodrug conversion to its active metabolites and to minimize chemotherapy side effects by reducing the prodrug dosage. Rational design, directed evolution, and phylogenetic methods are some approaches to developing tailored CYP enzymes for cancer therapy. Here, we provide a compilation of genetic modifications performed on CYP enzymes aiming to build highly efficient therapeutic genes capable of bio-activating different chemotherapeutic prodrugs. Additionally, this review summarizes promising preclinical and clinical trials highlighting engineered CYP enzymes’ potential in GDEPT. Finally, the challenges, limitations, and future directions of using CYP enzymes for GDEPT in cancer gene therapy are discussed.

Item Type: Article
Subjects: GO for STM > Medical Science
Depositing User: Unnamed user with email support@goforstm.com
Date Deposited: 24 May 2024 08:49
Last Modified: 24 May 2024 08:49
URI: http://archive.article4submit.com/id/eprint/2853

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