Module-combinatorial design and screening of multifunctional polymers based on polyaspartic acid for DNA delivery.
Int J Pharm
; 661: 124350, 2024 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-38885780
ABSTRACT
It is crucial to develop non-viral gene vectors that can efficiently and safely transfect plasmid DNA into cells. Low transfection efficiency and high cytotoxicity of cationic polymers hinder their application as gene carriers. Modification of cationic polymers has emerged as an attractive strategy for efficient and safe nucleic acids delivery. In this study, a simple and rapid method is developed to synthesize a series of multifunctional polymers by utilizing biodegradable polyaspartic acid as the backbone and modifying it with three modules. This one-component polymer possesses capabilities for nucleic acid condensation, cellular uptake, and endosomal escape. Polymers containing imidazole, triazole, or pyridine group exhibited promising transfection activity. Substituted with dodecylamine or 2-hexyldecan-1-amine enhance cellular uptake and subsequent transfection. Furthermore, the influence of ionizable amine side chains on gene delivery is investigated. Two optimal polymers, combined with the avian encephalomyelitis virus (AEV) plasmid vaccine, induced robust specific antibody responses and cellular immune responses in mice and chickens. Through module-combination design and screening of polyaspartamide polymers, this study presents a paradigm for the development of gene delivery vectors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Plasmids
/
Polymers
/
DNA
/
Transfection
/
Gene Transfer Techniques
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Int J Pharm
Year:
2024
Document type:
Article
Affiliation country: