Block Copolymer/Plasmid DNA Micelles Postmodified with Functional Peptides via Thiol-Maleimide Conjugation for Efficient Gene Delivery into Plants
- Biomacromolecules. 2019 Feb 11;20(2):653-661. doi: 10.1021/acs.biomac.8b01304.
- 1. Biomacromolecules Research Team , RIKEN Center for Sustainable Resource Science , 2-1 Hirosawa , Wako-shi , Saitama 351-0198 , Japan.
Introducing exogenous genes into plant cells is essential for a wide range of applications in agriculture and plant biotechnology fields. Cationic peptide carriers with cell-penetrating and DNA-binding domains successfully deliver exogenous genes into Plants. However, their cell-penetrating activity may be attenuated by undesired electrostatic interactions between the cell-penetrating peptide (CPP) domain and DNA cargo, resulting in limited gene delivery efficiency. Here, we developed the block copolymer maleimide-conjugated tetra(ethylene glycol) and poly(l-lysine) (MAL-TEG-PLL). Through electrostatic interactions with plasmid DNA (pDNA), MAL-TEG-PLL formed a micelle that presented maleimide groups on its surface. The micelle enabled postmodification with cysteine-containing functional peptides, including a CPP (BP100-Cys) and nuclear localization signal (Cys-NLS) via thiol-maleimide conjugation, thereby avoiding undesired interactions. According to a comparison of gene delivery efficiencies among the peptide-postmodified micelles, the amount of BP100-Cys on the micelle surface was key for efficient gene delivery. The BP100-postmodified micelle showed more efficient delivery compared with that of the BP100-premodified micelle. Thus, postmodification of polymeric micelles with functional peptides opens the door to designing highly efficient plant gene delivery systems.