In early 2022, Science published a breakthrough study as its cover article: researchers at the University of Pennsylvania Perelman School of Medicine used a single mRNA injection to achieve CAR-T therapy in mouse models of heart failure, successfully restoring cardiac function. This underscores that mRNA technology—which gained fame through COVID-19—holds significant potential across multiple disease areas, including oncology, heart disease, rare diseases, and autoimmune disorders.

Oncology

Cancer remains the world's leading cause of death. According to a December 2021 JAMA Oncology study, global new cancer cases increased from 18.7 million in 2010 to 23.6 million in 2019—a 26.3% rise—while cancer deaths rose from 8.29 million to 10.0 million, a 20.9% increase.

mRNA technology has long been explored for cancer treatment. Even before the pandemic, mRNA oncology pipelines were extensive, covering melanoma, prostate, colorectal, ovarian, breast, and lung cancers. mRNA cancer vaccines generate tumor-specific antigens via Dendritic Cells (DCs) , activating antigen-specific T cells for targeted tumor killing. Advantages include encoding multiple neoantigens, acting as self-adjuvants, rapid development, and personalized precision therapy.

BioNTech's BNT111, which received FDA Fast Track designation, encodes four TAAs (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE) expressed in over 90% of melanoma patients. Combined with PD-1 inhibitors, it prevents T cell exhaustion and improves outcomes in advanced melanoma.

Infectious Diseases

mRNA technology gained global recognition through COVID-19 vaccines. Moderna's mRNA-1273 and Pfizer–BioNTech's BNT162b2 both demonstrated >90% efficacy against symptomatic infection in clinical trials. Although breakthrough infections have increased with Delta and Omicron variants, protection against hospitalization and death remains robust. A May 2022 Nature Communications study of nearly 4 million U.S. individuals found both vaccines highly effective against severe disease within 90 days of full vaccination.

Influenza—causing 290,000–650,000 deaths annually—is another key target. Traditional egg-based flu vaccines have long production times and purification challenges; mRNA offers rapid production and flexibility. Pfizer, Sanofi, BioNTech, and Moderna are all developing mRNA flu vaccines, with candidates showing good safety and strong immunogenicity in early trials.

Chronic Diseases

The Penn study showed that a single mRNA injection could significantly reduce cardiac fibrosis and restore heart function in mice. In 2013, Moderna reported that intramuscular injection of VEGF-A mRNA expanded endogenous cardiac progenitor cells in mouse models. In November 2021, Moderna and AstraZeneca's AZD8601 Phase IIa trial met safety and tolerability endpoints in patients with stable coronary artery disease and moderately reduced LVEF, with no deaths or treatment-related SAEs.

mRNA is also being explored for cystic fibrosis and rare diseases, including Moderna's mRNA-3704 for methylmalonic acidemia and Translate Bio's MRT-5005 for cystic fibrosis—both in clinical trials.

While mRNA holds enormous promise across multiple diseases, it remains a challenging target. The "last mile" of accessibility and affordability still requires further effort.