Gene Delivery Systems and Therapeutic Applications

Gene delivery has emerged as a cornerstone of modern biomedicine, enabling targeted intervention at the molecular level for a spectrum of diseases. Delivery platforms fall broadly into viral and non-viral systems. Viral vectors, notably adeno-associated virus (AAV) and lentivirus, offer efficient cellular entry and sustained gene expression but present challenges in immunogenicity and payload capacity. Non-viral approaches—including lipid nanoparticles (LNPs), polymeric carriers and nucleic acid bioconjugates—have matured rapidly, providing flexible, scalable routes to transport RNA, DNA or gene-editing machinery. Critical considerations span carrier design, nucleic acid stability, cellular uptake, endosomal escape and tissue tropism. Advances in carrier chemistry, nucleotide modification and formulation have overcome many obstacles to in vivo delivery, underpinned by progress in codon optimisation, ionisable lipids and receptor-targeting ligands. Therapeutic applications encompass prophylactic and therapeutic vaccines, gene silencing via RNA interference, antisense oligonucleotide therapies, gene replacement for inherited disorders, and precision gene editing using CRISPR-based systems. Clinically approved products now include mRNA vaccines for infectious disease, small interfering RNA (siRNA) drugs for metabolic conditions and AAV-based therapies for rare genetic disorders. The convergence of improved delivery technologies with a deepening understanding of disease biology promises to broaden access to curative interventions, addressing unmet medical needs in oncology, neurology, cardiovascular disease and beyond.

Research from Nature Portfolio

Recent studies have demonstrated the power of algorithmic design in enhancing messenger RNA stability and immunogenicity. A computational approach borrowed from linguistic parsing has enabled the rapid identification of mRNA sequences with optimised secondary structure and codon usage, markedly extending half-life and amplifying protein expression. In preclinical models, these designs increased antibody titres by over a hundredfold compared with conventional codon-optimised constructs, illustrating a route towards more potent mRNA therapeutics. Complementing this, an analysis of the current landscape of nucleic acid therapeutics has delineated four platform technologies—antisense oligonucleotides, ligand-conjugated siRNA, lipid nanoparticles and viral vectors—highlighting their respective roles in clinical translation. This review has underscored the rationale behind each delivery paradigm, illustrated technological innovations that have driven approval of multiple genetic drugs and provided case studies of tissue-specific delivery bioconjugates, messenger RNA treatments and gene-editing modalities, thereby charting a roadmap for next-generation genetic medicines.

Gene Delivery Systems and Therapeutic Applications publication trend

The graph below shows the total number of articles in gene delivery systems and therapeutic applications across all publications each year (not limited to Nature Index journals).

Technical terms

Lipid nanoparticle (LNP): A nanoscale vesicle composed of ionisable and helper lipids, used to encapsulate and protect nucleic acids for cellular delivery.

Messenger RNA (mRNA): A single-stranded nucleic acid that encodes proteins, used in vaccines and protein replacement therapies.

Small interfering RNA (siRNA): Short double-stranded RNA molecules that induce sequence-specific gene silencing via the RNA interference pathway.

Adeno-associated virus (AAV): A non-pathogenic viral vector widely employed for stable gene delivery in vivo, with limited immunogenicity and defined tissue tropism.

CRISPR-Cas9: An RNA-guided nuclease system enabling precise genome editing by creating targeted DNA double-strand breaks for gene correction or disruption.

References

1. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature (2023).
2. The current landscape of nucleic acid therapeutics. Nature Nanotechnology (2021).
3. Lipid NanoparticlesFrom Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS Nano (2021).
4. Therapeutic siRNA: state of the art. Signal Transduction and Targeted Therapy (2020).