Challenges and Opportunities in Gene Delivery - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 51

Figure 2.1 Extracellular barriers in gene delivery following in vivo administration. The vector
system should be soluble and injectable; avoid adhesion (nonspecific binding) to tissues,
aggregation, embolization, and phagocytosis; extravasate and find a way to the inside of the
target cell to reach the nucleus.
(Taken with permission from Nishikawaa, M.T., Takakuraa, Y., and Hashidab, M. (2005).
Advanced Drug Delivery Reviews , 57, 675-688).
2.3.1 Extracellular Barriers for Naked DNA Delivery
The significance of various extracellular barriers depends on the cells to be targeted
and hence the route of administration of the DNA delivery system. The extent of
extracellular barriers was found to be significantly lower after local DNA administra-
tion by direct tissue injection because of direct organ and cell accessibility for trans-
gene expression as compared to the systemic in vivo DNA delivery after intravenous
injection. Early reports of transgene expression in locally accessible tissues such as
skeletal muscles, liver, skin, [23-29] , and so on, suggests efficient transgene expres-
sion after direct tissue injection of naked plasmid DNA. However, after systemic