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Since the pioneering discovery by Felgner et al. (1987) that cationic lipid
can efficiently transfect cells, there was a surge of research activity in this
area. The field received another boost when Nabel et al. (1993) successfully
completed a small phase I clinical trial in gene therapy of melanoma
using cationic liposome as a vector. The data strongly suggest that non-viral
vectors may be efficacious and safe in humans. Since then, many different
cationic lipids and polymers have been developed as vectors, some of them
also entered into clinical trials and others became commercial transfection
agents.
An equally important event occurred in 1990 (Wolff et al.). The work
indicated that naked DNA can transfect muscle cells when injected
intramuscularly. This is the beginning of using physical methods to introduce
DNA into cells. Since then, all major physical techniques, including pressure,
electricity, sound, light, heat, and particle bombardment, have been attempted.
Some of these methods are quite efficient. For example, the hydrodynamic
injection methods developed independently by Zhang et al., 1998 and Liu et al.,
1998, is the best method of transfecting liver cells among all viral and non-viral
vectors.
There was also much progress made in the molecular biological design
of the transgene expression system. For example, site-specific integration of the
transgene is now possible for prolonged gene expression without the threat of
insertional mutagenesis.
Since the publication of the first edition of Non-viral Vectors for Gene
Therapy in 1999, the field has experienced significant progress in both chemical
and physical vectors. More importantly, many mechanistic studies have
appeared to address how the vector works and why the vector produces
toxicity. It is safe to state that 18 years after the Felgner’s publication, the field
of non-viral vector for gene therapy is approaching maturity.
Due to much expansion of the field, it is not possible to include
all chapters of this edition in a single book. The two volumes are roughly
divided into chemical and physical methods emphasizing mechanistic aspects
of the vector. The new edition is then ended with a high note of delivering
siRNA for therapeutic purpose. RNA interference is definitely a new dimension
in non-viral gene therapy which will attract much attention in the years to
come. |
