Integrating mitosis, toxicity, and transgene expression in a telecommunications packet-switched network model of lipoplex-mediated gene delivery

Timothy M. Martin, Beata J. Wysocki, Jared P. Beyersdorf, Tadeusz A Wysocki, Angela K Pannier

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Gene delivery systems transport exogenous genetic information to cells or biological systems with the potential to directly alter endogenous gene expression and behavior with applications in functional genomics, tissue engineering, medical devices, and gene therapy. Nonviral systems offer advantages over viral systems because of their low immunogenicity, inexpensive synthesis, and easy modification but suffer from lower transfection levels. The representation of gene transfer using models offers perspective and interpretation of complex cellular mechanisms, including nonviral gene delivery where exact mechanisms are unknown. Here, we introduce a novel telecommunications model of the nonviral gene delivery process in which the delivery of the gene to a cell is synonymous with delivery of a packet of information to a destination computer within a packet-switched computer network. Such a model uses nodes and layers to simplify the complexity of modeling the transfection process and to overcome several challenges of existing models. These challenges include a limited scope and limited time frame, which often does not incorporate biological effects known to affect transfection. The telecommunication model was constructed in MATLAB to model lipoplex delivery of the gene encoding the green fluorescent protein to HeLa cells. Mitosis and toxicity events were included in the model resulting in simulation outputs of nuclear internalization and transfection efficiency that correlated with experimental data. A priori predictions based on model sensitivity analysis suggest that increasing endosomal escape and decreasing lysosomal degradation, protein degradation, and GFP-induced toxicity can improve transfection efficiency by three-fold. Application of the telecommunications model to nonviral gene delivery offers insight into the development of new gene delivery systems with therapeutically relevant transfection levels.

Original languageEnglish (US)
Pages (from-to)1659-1671
Number of pages13
JournalBiotechnology and Bioengineering
Volume111
Issue number8
DOIs
StatePublished - Jan 1 2014

Fingerprint

Telecommunications
Packet networks
Transgenes
Mitosis
Telecommunication
Transfection
Toxicity
Genes
Gene Transfer Techniques
Tissue Engineering
Genomics
Green Fluorescent Proteins
HeLa Cells
Genetic Therapy
Proteolysis
Proteins
Gene transfer
Gene therapy
Degradation
Gene encoding

Keywords

  • HeLa
  • Nonviral gene delivery
  • Nuclear plasmids
  • Packet-switched network
  • Telecommunication modeling
  • Transfection

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Integrating mitosis, toxicity, and transgene expression in a telecommunications packet-switched network model of lipoplex-mediated gene delivery. / Martin, Timothy M.; Wysocki, Beata J.; Beyersdorf, Jared P.; Wysocki, Tadeusz A; Pannier, Angela K.

In: Biotechnology and Bioengineering, Vol. 111, No. 8, 01.01.2014, p. 1659-1671.

Research output: Contribution to journalArticle

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