Challenges and Opportunities in Gene Delivery - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 44

2

Challenges and Opportunities in
Gene Delivery

Kaustubh Anil Jinturkar, Ambikanandan Misra
Pharmacy Department, TIFAC - Centre of Relevance and Excellence in New
Drug Delivery Systems, The Maharaja Sayajirao University of Baroda,
PO Box 51, Kalabhavan, Vadodara 390 001, Gujarat, India

2.1 Introduction

Genes are biological units of heredity, the building blocks of life, and direct the
production of protein that makes up a cell's structure and operates its vital chem-
istry. A genetic disorder is a disease caused by abnormalities in an individual's
genetic material (genome). Human genetic diseases occur because of the muta-
tion or deletion of genes impairing the normal metabolic pathways, ligand/receptor
function, regulation of cell cycle, structure, and function of cytoskeletal or extra-
cellular proteins. The four different types of genetic disorders observed are single
gene, multifactorial, chromosomal, and mitochondrial. The diseases that can be
suitably treated and managed by gene therapy are either hereditary or acquired dis-
eases. Hereditary diseases are normally caused by a single gene mutation or dele-
tion, but no single gene can be singly pointed out for development and prognosis
of acquired diseases. However, single transgene delivery with desired expression
delivered suitably by a gene delivery system to the target cell can significantly
improve the disease state. Some examples of hereditary and acquired diseases are
listed in Table 2.1 .
With increased understanding of advanced cellular and molecular biology, treat-
ment of these genetic diseases has become more practical by correcting the mutated
genetic sequence or by inserting the deleted sequence. Significant occurrence of
genetic diseases has motivated researchers to create more gene-based therapeutics
for better patient management and cure. Gene therapy is a term that can be applied
to any clinical therapeutic procedure in which genes are intentionally introduced into
human somatic cells for turning on or restoring a gene function (gain of function) in
order to produce a therapeutic protein with desired action. However, successful gene
therapy requires a convenient and patient-acceptable route of gene administration,
control over the location, functioning and expression of the administered gene, and
formulation of a stable and safe gene product with high robustness and acceptable
cost/risk-benefit ratio [15-18] .