Gene Delivery Using Chemical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 126

4

Gene Delivery Using Chemical
Methods

Jigar Lalani, Ambikanandan Misra
Pharmacy Department, The Maharaja Sayajirao University of Baroda,
PO Box 51, Kalabhavan, Vadodara 390 001, Gujarat, India

4.1 Introduction

The bottleneck of gene therapy is the development of a method by which a therapeu-
tic gene can be delivered to a cell site where gene expression can be accomplished.
The process of introducing a gene into cells for the purpose of gene expression is
called transfection. A number of methods have been developed for transfecting
eukaryotic cells. These can be classified as either viral or nonviral. The ideal method
for gene delivery should fulfill three basic requirements:

1. Protect against enzymatic degradation in the intracellular environment,
2. Transport the transgene across the plasma membrane and into the nucleus of the target cell,
and
3. Be devoid of any immunogenic response.

Viruses have the inherent or acquired ability to infect host cells and thus are capa-
ble of introducing foreign material into them. So, although viral delivery systems are
much more efficient in the delivery of genetic material, detrimental effects such as
toxicity, immunogenicity, acute immune response, and possible integration of viral
genetic material into the human genome outweigh the benefits achieved [1-6] .
Moreover, high costs involved in the production and packaging of viral particles
and strict regulatory guidelines have diverted focus toward development of nonvi-
ral vectors for gene delivery. Chemically defined nonviral vectors potentially avoid
the drawbacks of viral delivery and can be developed and manufactured in a simple
manner, similar to that of traditional pharmaceuticals. Nonviral gene delivery can be
divided into physical (carrier-free gene delivery) and chemical methods (synthetic
vector-based gene delivery). Chemical methods offer the advantage of simplic-
ity, ease of production, and low toxicity over viral and nonviral gene delivery using
physical methods. The term nonviral vector is broadly used for a chemical-mediated
nonviral vector.