Targeting mRNA therapeutics: current approaches and emerging platforms

Nucleic Acid Insights 2026; 3(3), 185–198

DOI: 10.18609/nai.2026.024

Published: 12 May
Review
Suman Pal, Rachelle C Canete, Jessica L Rouge

mRNA therapeutics is a rapidly expanding area of research within various medical applications, ranging from vaccines to cancer treatments. First widely adopted into the mainstream as a prevention tool for avoiding severe illness from SARS Cov2, mRNA is now being explored as a way to address genetic disorders and various forms of cancer. By encoding CRISPR machinery to be translated into cells or by training the immune system to attack cancerous cells, mRNA is fast becoming a powerful treatment tool for gaining access to traditionally undruggable targets. As the formulation chemistries that enable mRNA to be effective at expressing therapeutic proteins race forward, there are two major challenges currently limiting its full clinical potential. The first is the generalized inability to effectively target mRNA to specific cell types using standard LNPs, and the second, even more limiting challenge, is mRNA’s inability to efficiently reach the cytosol of cells once targeted to a specific cell type. Here, we will review aspects of the first challenge with regard to current methods of targeting mRNA, introducing new emerging platforms that seek to incorporate antibodies, aptamers, and small molecules as targeting agents. We highlight ways in which these critical challenges are being addressed and what future formulation designs seek to enable in order to achieve a more controlled delivery of this important biomolecule. 

Standard LNPs deliver mRNA predominantly to the liver with only 2–10% reaching the cytosol. This review covers emerging strategies to achieve targeted, controlled mRNA delivery.

01
How passive and active strategies redirect mRNA to specific tissues
02
How antibodies, aptamers, and small molecules enable cell-specific uptake
03
How stimuli-responsive nanocarriers control when and where mRNA is released
1
Passive targeting via lipid chemistry
2
Active targeting via ligand conjugation
3
Stimuli-responsive release
4
Cytosolic delivery & protein expression


Lipid chemistry governs biodistribution — head group, charge, and tail modifications can redirect LNPs to specific tissues without surface conjugation


Active targeting ligands increase cell-specific uptake but can alter LNP stability and transfection efficiency


Stimuli-responsive systems triggered by pH, ROS, ultrasound, or enzymes restrict mRNA release to the target microenvironment
mRNA Therapeutics
LNPs
Non-viral Delivery
Drug Targeting
Nucleic Acid Delivery