Identifying intracellular pDNA losses from a model of nonviral gene delivery

Timothy Michael Martin, Beata Joanna Wysocki, Tadeusz Antoni Wysocki, Angela K. Pannier

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Nonviral gene delivery systems are a type of nanocommunication system that transmit plasmid packets (i.e., pDNA packets) that are programmed at the nanoscale to biological systems at the microscopic cellular level. This engineered nanocommunication system suffers large pDNA losses during transmission of the genetically encoded information, preventing its use in biotechnological and medical applications. The pDNA losses largely remain uncharacterized, and the ramifications of reducing pDNA loss from newly designed gene delivery systems remain difficult to predict. Here, the pDNA losses during primary and secondary transmission chains were identified utilizing a MATLAB model employing queuing theory simulating delivery of pEGFPLuc transgene to HeLa cells carried by Lipofectamine 2000 nonviral DNA carrier. Minimizing pDNA loss during endosomal escape of the primary transmission process results in increased number of pDNA in the nucleus with increased transfection, but with increased probability of cell death. The number of pDNA copies in the nucleus and the amount of time the pDNAs are in the nucleus directly correlates to improved transfection efficiency. During secondary transmission, pDNAs are degraded during distribution to daughter cells. Reducing pDNA losses improves transfection, but a balance in quantity of nuclear pDNA, mitosis, and toxicity must be considered in order to achieve therapeutically relevant transfection levels.

Original languageEnglish (US)
Article number7018941
Pages (from-to)455-464
Number of pages10
JournalIEEE Transactions on Nanobioscience
Volume14
Issue number4
DOIs
StatePublished - Jun 1 2015

Keywords

  • Biological systems modeling
  • communication networks
  • molecular communication
  • nanobioscience
  • nonviral gene delivery
  • pDNA packet loss

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmaceutical Science
  • Computer Science Applications
  • Electrical and Electronic Engineering

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