NCRIS Turbo-Charges New mRNA Drugs

Therapeutics that use mRNA are a growing area of development and function by introducing the “message” to make a therapeutic protein into the patient’s body, instead of the protein itself. This approach can revolutionise the fight against many kinds of cancers, genetic and infectious diseases.

Conventional strategies deliver mRNA drugs to tissues inside lipid nanoparticles (LNPs). These naturally tend to accumulate in the liver, making it easy to target liver diseases. Directing these LNPs to other tissues often involves surface modifications that compromise manufacturing scalability, affect particle size, and can trigger unwanted immune responses. These limitations currently confine the use of mRNA-LNPs primarily to liver diseases, restricting the broader application of this potentially life-saving technology to conditions affecting other parts of the body.

In a recent breakthrough study, researchers from the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland, demonstrated a flexible and efficient approach for targeting mRNA delivery using bispecific antibodies (BsAbs). This directs mRNA-LNPs to the types of cells that carry the specific surface proteins recognised by the antibodies. Promising results for sustained and selective delivery to tumour tissues were seen both in-vitro and in-vivo, while minimising off-target accumulation in organs like the liver.

Ms Bettina Dietmair, PhD Student, BASE Facility, AIBN Image Credit: BASE Facility

To realise this work, the research team leveraged advanced research infrastructure and technical expertise from four NCRIS* providers:

• The Australian National Fabrication Facility (ANFF) provided access to confocal microscopy systems and user training. Imaging was performed on a Zeiss® LSM® 710 inverted laser scanning confocal microscope at their Queensland node. These resources were essential to evaluate mRNA delivery efficiency and specificity in different cell types.
• Microscopy Australia, through its UQ facility, delivered specialised cryo-transmission electron microscopy (cryo-TEM) expertise to reveal the morphology and structural integrity of LNPs and BsAb complexes, particularly to assess how surface functionalisation impacted particle behaviour.
• The National Imaging Facility (NIF) played a pivotal role in the in vivo evaluation of targeting strategies. Non-invasive animal imaging allowed researchers to track luciferase mRNA expression and confirm the successful delivery of mRNA-LNPs to tumour tissues.
• Therapeutic Innovation Australia (TIA) supported access to high-quality mRNA-LNP formulations through the BASE Facility. The BASE Facility team manufactured the mRNA-LNPs critical for both in vitro and in vivo

By combining these world-class capabilities, the project was able to move swiftly from conceptual development to experimental validation, confirming the benefits of targeting over conventional approaches in both cellular and animal models. The ability to adapt BsAb for different target antigens creates a modular delivery platform with broad therapeutic potential.

This study sets the stage for more efficient, precise, and safer mRNA-based treatments for cancer and other diseases that require tissue-specific targeting. With scalable infrastructure already available across Australia’s NCRIS network, the findings could accelerate pre-clinical and translational development of mRNA therapeutics tailored for individual diseases and patient populations.

*National Collaborative Research Infrastructure Strategy

B. Deitmair et al., Molecular Therapy Nucleic Acids 2025
DOI: 10.1016/j.omtn.2025.102520