Scalable Purification of Plasmid DNA Nanoparticles by Tangential Flow Filtration for Systemic Delivery

Heng Wen Liu, Yizong Hu, Yong Ren, Hwanhee Nam, Jose Luis Santos, Shirley Ng, Like Gong, Mary Brummet, Christine A. Carrington, Christopher G. Ullman, Martin G. Pomper, Il Minn, Hai Quan Mao

Research output: Contribution to journalArticlepeer-review


Plasmid DNA (pDNA) nanoparticles synthesized by complexation with linear polyethylenimine (lPEI) are one of the most effective non-viral gene delivery vehicles. However, the lack of scalable and reproducible production methods and the high toxicity have hindered their clinical translation. Previously, we have developed a scalable flash nanocomplexation (FNC) technique to formulate pDNA/lPEI nanoparticles using a continuous flow process. Here, we report a tangential flow filtration (TFF)-based scalable purification method to reduce the uncomplexed lPEI concentration in the nanoparticle formulation and improve its biocompatibility. The optimized procedures achieved a 60% reduction of the uncomplexed lPEI with preservation of the nanoparticle size and morphology. Both in vitro and in vivo studies showed that the purified nanoparticles significantly reduced toxicity while maintaining transfection efficiency. TFF also allows for gradual exchange of solvents to isotonic solutions and further concentrating the nanoparticles for injection. Combining FNC production and TFF purification, we validated the purified pDNA/lPEI nanoparticles for future clinical translation of this gene nanomedicine.

Original languageEnglish (US)
Pages (from-to)30326-30336
Number of pages11
JournalACS Applied Materials and Interfaces
Issue number26
StatePublished - Jul 7 2021


  • DNA nanoparticles
  • biocompatibility
  • gene delivery
  • linear PEI
  • tangential flow filtration

ASJC Scopus subject areas

  • General Materials Science


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