Biomedical Engineering Reference
In-Depth Information
in elucidating the role of bradykinin B
1
and B
2
receptors in the central regulation of
blood pressure
[253]
.
7.9.8 Viral Infections
It has always been difficult to design and develop antiviral drugs with low toxic-
ity and improved specificity. A rational strategy to fight against viral diseases is to
inhibit the genes implicated in various viral infections with the help of AS ODNs.
Antisense technology can be easily applied to viruses as they encode unique proteins,
very different from the ones encoded by normal cells. Vitravene
®
(fomivirsen) was
the first antiviral AS ODN used intravitreally to treat cytomegalovirus retinitis
[10]
.
The various viruses being investigated as potential targets of antisense drugs include
human papillomavirus
[255]
, human immunodeficiency virus-2 (HIV-2)
[256]
, hepa-
titis-B virus
[257]
, influenza A virus
[258]
, and herpes simplex virus (HSV)
[259]
.
Traditional antiviral drugs are competitive antagonists binding to the disease-causing
proteins and subsequently blocking the actions of natural agonists, resulting in tox-
icological manifestations. Viral proteins essential for the replication of viruses are
the prime targets of these antisense drugs. AS ODNs, being selective and specific,
readily bind to the target mRNA sequence, thereby downregulating the expression of
related proteins and causing the death of the virus.
7.10 Benefits of Antisense Drugs in Therapeutics
Antisense molecules that mediate RNAi can be synthesized chemically in the labora-
tory and then introduced into cells to achieve targeted gene silencing. This opens up
enormous possibilities for using these as potential drug candidates. Following are the
key features highlighting the advantages of antisense technology, specifically siRNA:
l
siRNA is a potent and highly specific therapeutic moiety
[5]
.
l
The traditional drugs have limited targets, whereas due to the completion of the human
genome project, antisense agents like siRNA can be designed for unlimited disease targets
[5,10,18,130]
.
l
Most of the drugs act for the symptomatic relief of the disease by inhibiting the disease-
causing factor. However, siRNA therapy does not allow the formation of disease-causing
elements and hence acts to remove the root cause of the disease
[5,10,18,130]
.
l
siRNA can be explored as a prophylactic agent for various known epidemic diseases.
l
Antisense technology can be utilized for the prevention and treatment of deadly diseases
like SAARS and swine flu, by sequence-specific design complementary to the disease-
causing genes of these viruses.
l
Some diseases are caused by mutation in a single allele of the gene, and siRNA can be
designed to act on that particular allele without affecting the normal allele
[5]
.
l
The difficulty in treating some viral diseases like HIV is the changing viral mutation. Thus,
a drug effective at a particular time will not be effective for the next viral mutation. siRNA
can be designed according to the particular gene mutation; moreover, a pool of more than
one mutant-specific siRNA can be incorporated in a single delivery agent for delivering at
one time
[18]
.
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