Content area
Full Text
Gene Therapy (2005) 12, 17341751
& 2005 Nature Publishing Group All rights reserved 0969-7128/05 $30.00www.nature.com/gtREVIEWIntracellular trafficking of nonviral vectorsLK Medina-Kauwe1,2, J Xie3 and S Hamm-Alvarez31Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Department of Medicine, David Geffen
School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; and3Department of Pharmaceutical Sciences,
University of Southern California, Los Angeles, CA, USANonviral vectors continue to be attractive alternatives to
viruses due to their low toxicity and immunogenicity, lack
of pathogenicity, and ease of pharmacologic production.
However, nonviral vectors also continue to suffer from relatively low levels of gene transfer compared to viruses, thus
the drive to improve these vectors continues. Many studies
on vectorcell interactions have reported that nonviral
vectors bind and enter cells efficiently, but yield low gene
expression, thus directing our attention to the intracellular
trafficking of these vectors to understand where the
obstacles occur. Here, we will review nonviral vector trafficking pathways, which will be considered here as the steps
from cell binding to nuclear delivery. Studies on the
intracellular trafficking of nonviral vectors has given us
valuable insights into the barriers these vectors must
overcome to mediate efficient gene transfer. Importantly,
we will highlight the different approaches used by researchers to overcome certain trafficking barriers to gene transfer,
many of which incorporate components from biological
systems that have naturally evolved the capacity to overcome such obstacles. The tools used to study trafficking
pathways will also be discussed.Gene Therapy (2005) 12, 17341751. doi:10.1038/
sj.gt.3302592; published online 4 August 2005Keywords: nonviral; trafficking; vector; cytoskeletonIntroductionNonviral vector development has incorporated diverse
technologies in attempts to mimic the efficient gene
delivery capacity of viruses. The low toxicity and
immunogenicity, lack of pathogenicity, and ease of
pharmacologic production continue to make nonviral
vectors an attractive alternative to viruses. However,
nonviral vectors also continue to suffer from relatively
low levels of gene transfer compared to viruses, thus the
drive to improve these vectors continues.Numerous studies on vectorcell interactions have
reported that nonviral vectors bind and enter cells
efficiently, but yield low gene expression. Our attention
has thus been directed to the intracellular trafficking of
these vectors to understand where the obstacles occur.
Indeed, critical barriers exist from the assembly of the
vector particle to its disassembly...