Gene delivery vectors

Gene Therapy - intro

• Gene therapy has emerged in the late 20th century
• An approach to treat serious human illnesses resistant to
traditional therapies.
• The basis of gene therapy is to cure genetic diseases by
introducing new genetic instructions into the tissues of
patients in order to compensate for abnormal or missing
genes or to convey a new function (Emery 2004).
• Until now, it has proven its usefulness in a number of
clinical trials aimed to develop a cure for several
inherited and acquired genetic diseases.
• The majority of the gene therapy clinical trials are
directed against
– cancer,
– cardiovascular,
– nervous system,
– eye or
– lung diseases

• there are several success stories in these trials (Biffi et

al. 2011; Leung et al. 2010; Stieger and Lorenz 2010).
 Examples
• In X-linked adrenoleukodystrophy (ALD), for example, a
lentiviral mediated therapy of hematopoietic stem cells
resulted in ALD protein production in two boys and the
disease was stabilized or improved (Cartier et al. 2009).
• Another clinical study with inherited retinal disease showed
that in treated blind children, adeno-associated viruses
carrying a normal RPE65 improved their visual fields
(Maguire et al. 2009).
• Retroviral transduction of hematopoietic stem cells carrying
ADA gene effectively protected eight children against
infections and improvement in physical development made a
normal lifestyle possible (Aiuti et al. 2009).
• Cancer which is another candidate for gene
therapy trials arises as a direct result of
genetic mutations. It is one of the leading
causes of mortality in the world today.
Therefore besides the classical types of cancer
therapy such as chemotherapy or
radiotherapy, it is feasible to use this novel
technology for the correction of this genetic
disease (Majhen and Ambriovic-Ristov 2006;
Wu et al. 2001).
• A variety of gene delivery vectors have been developed in the last
decade and the success of gene therapy is largely dependent on
the gene delivery methodology which can be divided into four
groups (Giacca 2010; Sakurai et al. 2007; Warnock et al. 2011):
• (i) Simple utilization of naked plasmid or short regulatory nucleic
acids by local administration.
• (ii) Facilitation of nucleic acid entry into the cells by physical
methods such as electroporation or sonoporation.
• (iii) Transport of nucleic acids into the cells by liposomes or
polymers.
• (iv) Embedding of nucleic acid sequences within the viral genomes.
• A variety of gene delivery vectors have been
developed in the last decade and the success of
gene therapy is largely dependent on the gene
delivery methodology which can be divided into
four groups (Giacca 2010; Sakurai et al. 2007;
Warnock et al. 2011):
(i) Simple utilization of naked plasmid or short regulatory
nucleic acids by local administration.
(ii) Facilitation of nucleic acid entry into the cells by physical
methods such as electroporation or sonoporation.
(iii) Transport of nucleic acids into the cells by liposomes or
polymers.
(iv) Embedding of nucleic acid sequences within the viral
genomes.