Cationic Polymers for the Delivery of Therapeutic Nucleotides - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 28

and delivery of therapeutically important nucleotides, e.g.,

DNA and siRNA. The mechanism and recent progress in cationic
polymer based gene delivery are reviewed in detail.

in vivo

2.1 Introduction

The basic concept of gene therapy is that disease can be treated
by transfer of genetic material into specific cells of a patient to
supplement defective genes responsible for disease development.
Stribley

demonstrated two strategies involved for the
application of gene delivery: (i) Corrective therapy — correction
of genetic defects in target cells — is exploited for the treatment
of diseases with single gene disorders like severe combined
immunodeficiency syndromes, cystic fibrosis, hemophilia, sickle
cell anemia, β-thalassemia, muscular dystrophy and lignant tumors,
including ovarian carcinoma, and (ii) cytotoxic gene therapy —
destruction of target cells using a cytotoxic pathway; it is used for
the treatment of malignant tumors, including ovarian, breast, and
endometrial carcinomas.

et al.

1

The fundamental idea is to deliver the gene to cells or tissues. It
may be activation, silencing, introducing or gene knock out and knock
down both in vitro and in vivo toward cells, and the possibilities for

2

interventions. Successful gene therapies depend on the efficient

delivery of genetic materials into the cell nucleus and its effective
expression within these cells. DNA can be delivered into the cell
nucleus either using physical means or by specific carriers that carry
the genes into the cells. Number of techniques has been developed
for DNA delivery, including direct introduction of transgene using
cell electroporation, microinjection of DNA, and incorporation of
the gene by vectors.

3
Vectors for delivering genes can be divided into two main
groups: (a) Viral carriers, where the DNA to be delivered is inserted
into a virus, and (b) cationic molecular carriers, which forms
electrostatic interactions with DNA for delivering gene to cells and
includes polymers and lipids. Viral vectors, including retroviruses,

adenoviruses, and adeno-associated viruses, are effectively used for
introducing genetic material into host cells,

4

5

but immunogenicity,
inflammatory effects, and safety concerns with use of these viruses
restrict their usefulness.