Biomedical Engineering Reference
In-Depth Information
7.1 Introduction
In the 1960s, thanks to the great strides aff orded by antibiotics and
vaccines, a general opinion that infectious diseases were a problem
of the past was beginning to emerge. In fact, then US Surgeon General
William H. Stewart has been widely cited as saying that it was “time
to close the topic on infectious diseases.” While it is refuted that
Stewart truly made such statements, the irrefutable fact is that the
war against infectious diseases is far from over; infectious agents
remain unconquered and are now the world's biggest killer of
children and young adults. They account for more than 13 million
deaths a year — one in two deaths in developing countries [123]. It
is estimated that over the next hour alone, 1,500 people will die from
an infectious disease—over half of them children under the age of
five. For 40 years now, we have been reminded time and time again of
the devastation that can be caused by classical re-emerging as well as
newly emerging pathogenic viruses. The most well-known examples
of this are the ongoing threat of influenza pandemics (estimated death
rates of 250,000-500,000/year) [121], the emergence of human
immunodeficiency virus (HIV) (a consistent annual death rate of 2
million), and the alarming epidemic caused by the newly emergent
severe acute respiratory syndrome (SARS) virus (774 deaths in the
2003 Epidemic) [120]. A plethora of agents of natural, chemical and
biological origins have been investigated for their potential to combat
these and other viral threats. One method that has been relatively
recently added to the arsenal against viral infections is based on the
natural biological phenomenon of RNA interference (RNAi).
As recently as 12 years ago, the paramount study of Andrew Fire
and Craig Mello [38] described for the first time, the mechanism of
RNAi. Using C. elegans as a model organism, this study identified the
biological mechanism where endogenous small double stranded
RNAs (dsRNA) mediated inhibition of gene expression by binding
larger messenger RNAs (mRNAs) at homologous sequences and
triggering their degradation. A few years later, exogenously added
short interfering RNAs (siRNAs) were experimentally shown to
trigger the same RNAi machinery in mammalian cells [16, 34]. After
extensive research we now know that longer (≥ 70 nucleotides)
dsRNAs are cleaved by the enzyme Dicer into the smaller ~19-21
nt-long siRNAs. The resulting siRNA is subsequently loaded onto
a RNA-induced silencing complex (RISC), where one strand of the
 
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