The liver is an attractive target tissue for gene therapy. Current tec
hniques which may be useful for in vivo hepatic gene delivery include
viral vectors such as retroviruses, adenoviruses and adeno-associated
viruses, and non-viral methods including liposome/DNA complexes, pepti
de/DNA complexes, dendrimer delivery and direct injection of DNA. Whil
e, previous studies have suggested that genes cannot be delivered to l
iver tissue by direct DNA injection, this review focuses on the factor
s that lead to significant gene expression in liver, as compared to ot
her tissues, after direct injection of plasmid DNA. Several factors ar
e discussed, including injection technique, DNA dose, DNA diluent and
enhancement of transfected gene expression by dexamethasone administra
tion. The current limitations and potential uses of direct DNA injecti
on into liver are reviewed. Direct DNA injection is currently a reliab
le, reproducible and simple alternative for hepatic gene transduction
that provides a tool for molecular research and may have future potent
ial for therapeutic gene delivery.