mRNA-Based Therapeutics in Cancer Treatment

Abstract

Over the past two decades, significant technological innovations have led to messenger RNA (mRNA) becoming a promising option for developing prophylactic and therapeutic vaccines, protein replacement therapies, and genome engineering. The success of the two COVID-19 mRNA vaccines has sparked new enthusiasm for other medical applications, particularly in cancer treatment. In vitro-transcribed (IVT) mRNAs are structurally designed to resemble naturally occurring mature mRNA. Delivery of IVT mRNA via delivery platforms such as lipid nanoparticles allows host cells to produce many copies of encoded proteins, which can serve as antigens to stimulate immune responses or as additional beneficial proteins for supplements. mRNA-based cancer therapeutics include mRNA cancer vaccines, mRNA encoding cytokines, chimeric antigen receptors, tumor suppressors, and other combination therapies. To better understand the current development and research status of mRNA therapies for cancer treatment, this review focused on the molecular design, delivery systems, and clinical indications of mRNA therapies in cancer.

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

“…MRNA, a large class of RNA molecules, could influence not only the transcription of genes at the transcription level but also the proteins that genes express. Factors affecting mRNA stability have been described in the reference ( Sun et al, 2023 ). A series of achievements have been made in the development of mRNA drugs and vaccines, such as the COVID-19 mRNA vaccines.…”

“…Abnormally altered genes in tumor cells can reduce drug uptake or promote drug efflux, or the conformation of tumor targets can be changed to cause drug resistance ( Heinrich et al, 2020 ). With the understanding of the mechanism of drug resistance to tumor immunotherapy, the following nanotechnology-based strategies have been proposed to improve the efficacy of tumor immunotherapy, such as generating neoantigens, tumor-specific antigens, immunomodulatory mRNA vaccines, mRNA-encoded antibodies and vaccines, and protein replacement derived from defective gene code products, etc ( Sun et al, 2023 ). The mechanisms of these strategies and their applications in the treatment of HCC have been described in the literature and will not be detailed here.…”

“…And the purified IVT mRNA by high-performance liquid chromatography (HPLC) and VSW-3 RNAP could effectively solve this problem ( Xia et al, 2022 ; Chehelgerdi and Chehelgerdi, 2023 ). To increase the stability of nucleic acid drugs, nucleic acid drugs are encapsulated to avoid contact with a complex internal environment ( Sun et al, 2023 ). mRNA was modified and codon-optimized to improve mRNA drug expression in target cells ( Chehelgerdi and Chehelgerdi, 2023 ).…”

Correlation Between Messenger RNA Expression and Clinicopathological Features of Breast Cancer: A systematic review

“…This includes methods such as regulating the expression levels of oncogenes and enhancing the function of tumor suppressor genes, aiming to achieve more precise and effective treatment for breast cancer. This opens up new avenues for developing novel treatment strategies and drugs 13 . In summary, the relationship between mRNA and breast cancer is a complex and highly researched area.…”

Scalable multimodal weak anion exchange chromatographic purification for stable mRNA drug substance

“…The recent COVID-19 pandemic triggered an unprecedented revolution in biomedicine that resulted in an emergence of messenger RNA (mRNA) as a modality with immense therapeutic potential demonstrated primarily by mRNA-1273 [1] and BNT162b2 [2] mRNA vaccines against SARS-CoV-2. Their potential clinical utility has furthermore been demonstrated in a wide number of recent studies in cancer [3][4][5], CRISPR-Cas9-based treatment [6], anaphylaxis [7], and rare diseases [8]. mRNA coding for antibody fragments has been shown as a potential replacement for monoclonal antibody-therapy [9].…”