Textbook of Personalized Medicine - Second Edition [2015]

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to the tumor suppressor gene p53, which frequently shows LOH in cancer cells
(Mook et al. 2009 ). Thus RNAi may play an important role in personalized medi-
cine. A few siRNAs are already in clinical trials. Role of RNAi in the development
of personalized medicine is shown in Fig. 9.1.

MicroRNAs

MicroRNAs (miRNAs), small and mostly non-coding RNA gene products, are mol-
ecules derived from larger segments of “precursor” RNA that are found in all diverse
multicellular organisms. miRNAs are 21–25 nucleotide transcripts that repress gene
function through interactions with target mRNAs. Polymorphisms in the miRNA
pathway are emerging as a powerful tool to study the biology of a disease and have
a potential to be used in disease prognosis and diagnosis. Detection of MiR-
polymorphisms holds promise in the fi eld of miRNA pharmacogenomics, molecular
epidemiology and for individualized medicine. MiRNA pharmacogenomics can be
defi ned as the study of miRNAs and polymorphisms affecting miRNA function in
order to predict drug behavior and to improve drug effi ciency. Advancements in the
miRNA fi eld indicate the clear involvement of miRNAs and genetic variations in the
miRNA pathway in the progression and prognosis of diseases such as cancer, hyper-
tension, cardiovascular disease, and muscular hypertrophy. Various algorithms are
available to predict miRNA-target mRNA sites are available. Polymorphisms that
may potentially affect miRNA-mediated regulation of the cell can be not only pres-
ent in the 3′UTR of a miRNA target gene, but also in the genes involved in miRNA
biogenesis and miRNA sequences. A polymorphism in processed miRNAs may
affect expression of several genes and have serious consequences.

RNAi

miRNA

Diagnostics

Therapeutics

Personalized medicine

Drug

discovery

Gene

therapy

Drug

delivery

siRNA

Fig. 9.1 Role RNAi in development of personalized medicine

9 Personalized Biological Therapies