Annealing of pDNA to Form the Single-Nucleobase-Terminal Complex for In Vivo Gene Expression
Although complexes with polycationic carriers have been proposed for the skeletal muscle delivery of plasmid DNA (pDNA), there is a problem in reducing the effect due to nonspecific aggregation in vivo caused by multiple cationic charges. Therefore, we have synthesized a thymine end-modified poly(ethylene glycol) (Thy-PEG) as a potentially nonionic single-nucleobase end-modified PEG and designed to form a complex by hydrogen bonding with pDNA whose duplex was partially dissociated by annealing. Then, the local administration of the resulting Thy-PEG/pDNA complex with a PEG chain length of 5k and a [Thy]<sub>Thy-PEG</sub>/[Base]<sub>pDNA</sub> ratio of 0.5 to the tibialis muscle of mice resulted in a tendency for a 14-fold increase in expression, as compared to that of annealed naked pDNA. In this study, the created Thy-PEG/pDNA complexes, that is, single-nucleobase-terminal complexes (SNTCs), can offer a unique cation-free pDNA delivery platform in vivo.
Authors
- Shoichiro Asayama (ORCID: https://orcid.org/0000-0002-5109-6052)
- Yoichi Negishi (ORCID: https://orcid.org/0000-0003-4364-8694)
- Yoko Endo-Takahashi
- Momoko Nakanishi
Institutions
- Tokyo University of Pharmacy and Life Sciences (JP)
- Tokyo Metropolitan University (JP)
Publication Details
- Journal
- ACS Applied Bio Materials
- Published
- 2026-01-16
- DOI
- https://doi.org/10.1021/acsabm.5c02207
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00