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Metabolite-Based Modification of Poly(l-lysine) for Improved Gene Delivery
- Source :
- Biomacromolecules. 21(9)
- Publication Year :
- 2020
-
Abstract
- Synthetic gene delivery systems employ multiple functions to enable safe and effective transport of DNA to target cells. Here, we describe metabolite-based poly(l-lysine) (PLL) modifiers that improve transfection by imparting both pH buffering and nanoparticle stabilization functions within a single molecular unit. PLL modifiers were based on morpholine (M), morpholine and niacin (MN), or thiomorpholine (TM). PLL modification with (MN) or (TM) imparted buffering function over the pH range of 5-7 both in solution and live cells and enhanced the stability of PLL DNA nanoparticles, which exhibited higher resistance to polyanion exchange and prolonged blood circulation. These properties translated into increased transfection efficiency in vitro coupled with reduced toxicity compared to unmodified PLL and PLL(M). Furthermore, PEG-PLL(MN) DNA nanoparticles transfected muscle tissue in vivo for >45 days following intramuscular injection. These polymer modifiers demonstrate the successful design of multifunctional units that improve transfection of synthetic gene delivery systems while maintaining biocompatibility.
- Subjects :
- Polymers and Plastics
Biocompatibility
Metabolite
Bioengineering
02 engineering and technology
Gene delivery
010402 general chemistry
Transfection
01 natural sciences
Polyethylene Glycols
Biomaterials
chemistry.chemical_compound
In vivo
Morpholine
Materials Chemistry
Polylysine
Gene Transfer Techniques
DNA
Genetic Therapy
021001 nanoscience & nanotechnology
0104 chemical sciences
Thiomorpholine
chemistry
Biophysics
0210 nano-technology
Subjects
Details
- ISSN :
- 15264602
- Volume :
- 21
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Biomacromolecules
- Accession number :
- edsair.doi.dedup.....194811690d8ba38d8bdb576edc32e18b