Medical Molecular Engineering of Nucleic Acids and Proteins

Advances in molecular biotechnology have transformed the therapeutic landscape by harnessing the unique recognition and functional capabilities of nucleic acids and proteins. Rational design of messenger RNA and oligonucleotide sequences now underpins vaccine development, gene editing and RNA interference, while directed evolution and structural engineering have yielded enzymes, antibodies and polypeptides with enhanced stability, specificity and pharmacokinetics. Lipid- and polymer-based nanoparticles protect nucleic acid cargos from degradation, enable cytosolic delivery and confer tissue selectivity, whereas peptide and protein scaffolds exploit stimulus-responsive behaviour to achieve controlled release or in-situ assembly. Concurrently, bioorthogonal chemistries permit site-specific conjugation of synthetic polymers to proteins, extending circulatory half-life and reducing immunogenicity. Together, these innovations facilitate precision interventions in oncology, infectious disease, inherited disorders and regenerative medicine, by translating molecular insights into targeted therapies with improved safety and efficacy.

Research from Nature Portfolio

In 2023, a novel algorithmic framework was reported that optimises mRNA secondary structure and codon usage simultaneously, yielding vaccine sequences with markedly increased stability and protein expression. In animal models, these designed mRNAs exhibited up to a hundredfold rise in serum half-life and elicited immune responses far exceeding conventional codon-optimised constructs, demonstrating a new paradigm for sequence-informed vaccine design. Earlier work in pancreatic cancer employed patient-specific mRNA–lipoplex vaccines encoding tumour-derived neoantigens alongside checkpoint blockade and chemotherapy. This regimen generated de novo expansion of high-avidity CD8⁺ T cells targeting multiple neoepitopes and correlated with prolonged recurrence-free survival, thereby validating personalised transcript vaccines in an aggressive tumour type. Complementing these advances, longitudinal profiling of plasma cell-free RNA has emerged as a robust liquid-biopsy tool. An eighteen-gene cfRNA panel measured at five to sixteen weeks of gestation can predict pre-eclampsia risk months before clinical onset, outperforming traditional risk factors and offering a non-invasive route to early intervention in high-risk pregnancies.

Medical Molecular Engineering of Nucleic Acids and Proteins publication trend

The graph below shows the total number of articles in medical molecular engineering of nucleic acids and proteins across all publications each year (not limited to Nature Index journals).

Technical terms

mRNA vaccine: A vaccine modality delivering messenger RNA encoding an antigen, enabling host cells to produce the target protein in situ and elicit immunity.

Neoantigen: A tumour-specific peptide arising from somatic mutations, not present in normal tissues, used to elicit personalised T cell responses.

Cell-free RNA (cfRNA): Extracellular RNA fragments in plasma reflecting gene expression in maternal, placental or foetal tissues, used as non-invasive biomarkers.

Lipid nanoparticle (LNP): Ionisable lipid-based vesicles formulated with helper lipids, cholesterol and PEG-lipid to encapsulate and deliver nucleic acids.

Elastin-like polypeptide (ELP): Genetically encoded biopolymer exhibiting reversible phase transitions with temperature, used for depot-forming drug conjugates.

Bioorthogonal chemistry: Chemical reactions that occur selectively in living systems without interfering with endogenous processes, facilitating site-specific bioconjugation.

References

1. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature (2023).
2. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature (2023).
3. Early prediction of preeclampsia in pregnancy with cell-free RNA. Nature (2022).
4. A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles. Advanced Materials (2023).
5. Thermoresponsive Polypeptide Fused L‐Asparaginase with Mitigated Immunogenicity and Enhanced Efficacy in Treating Hematologic Malignancies. Advanced Science (2023).