Next-Generation Non-Viral Vectors for Gene Therapy and DNA Vaccination

Dear Colleagues,

The field of gene therapy continues to experience rapid innovation, particularly in terms of the development of non-viral vectors that offer safer, scalable, and more versatile alternatives to viral systems. Building upon the success of our previous Special Issue, entitled “Plasmid DNA for Gene Therapy and DNA Vaccine Applications”,  and “Plasmid DNA for Gene Therapy and DNA Vaccine Applications, 2nd Edition", which highlighted the central role played by plasmid DNA, this new volume aims to broaden the thematic scope to include new vector platforms that are reshaping the landscape of non-viral gene therapy and DNA vaccination.

Plasmid DNA remains a fundamental tool in gene therapy and DNA vaccine development due to its adaptability, safety profile, and relatively straightforward manufacturing processes. Innovations in plasmid design, backbone minimization, codon optimization, and advanced delivery technologies have significantly enhanced its therapeutic potential. However, the field is now witnessing a notable shift towards fully synthetic, next-generation non-viral vectors. Synthetic DNA vectors produced via enzymatic or PCR-based methods eliminate the need for bacterial propagation and antibiotic resistance genes, enabling greater control over vector composition and purity. These features align well with the current regulatory expectations for clinical-grade therapeutics.

In parallel, synthetic mRNA vectors have emerged as compelling platforms with distinct advantages due to their transient expression profiles and inherent ability to engage the host's translational machinery without the need for nuclear entry. Their success in mRNA vaccine platforms has paved the way for broader therapeutic applications, including cancer immunotherapy, protein replacement therapies for genetic disorders, and genome editing delivery.

Furthermore, novel delivery systems, such as lipid nanoparticles, polymeric carriers, exosome-based delivery, and physical methods like gene electrotransfers, continue to evolve, addressing key challenges in terms of cellular uptake, endosomal escape, and tissue-specific targeting. These advances are critical to improving therapeutic efficacy while maintaining safety.

Expanding the toolbox of non-viral gene therapy is critical to advancing precision medicine and addressing unmet clinical needs. Achieving this requires continued multidisciplinary collaboration to refine vector design, improve delivery efficiency, and ensure safety and efficacy in diverse therapeutic applications. Furthermore, aligning technological advances with regulatory frameworks will be key to facilitating the translation of these promising platforms from the laboratory to the clinic.

This Special Issue welcomes the submission of original research articles and reviews exploring the full spectrum of non-viral vectors for gene therapy and DNA vaccination. Topics of interest include, but are not limited to, the following:

- Design of plasmid DNA, mRNA, and synthetic DNA vectors;

- Innovations in the cell-free production of non-viral vectors;

- Advances in physical, chemical, and biological delivery systems;

- Mechanistic insights into cellular uptake, trafficking, and gene expression;

- Preclinical and clinical evaluations of non-viral gene therapy strategies;

- Manufacturing, scalability, and regulatory considerations;

- Integration of non-viral vectors with immunomodulation and targeted therapies.

We look forward to receiving your valuable contributions and to facilitating a comprehensive discussion on the evolving landscape of non-viral gene therapy vectors.

Dr. Urska Kamensek
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• non-viral vectors
• gene therapy
• DNA vectors
• plasmid vectors
• mRNA vectors
• lipid nanoparticles (LNPs)
• cell-free DNA synthesis
• gene electrotransfer
• targeted gene delivery
• non-viral vector manufacturing
• clinical translation of gene therapies