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Clinical Pharmacy in the Genomic Era
modified to provide control for gene expression.
One of the greatest discoveries of recent years is that
RNA molecules are not simply intermediates for
translation to protein but that in their many different
guises, they have many different functions in gene
expression (15). MicroRNAs have attracted significant
attention, and understanding their in-vivo processing
(Figure 2) is leading to the development of new classes of
medicines such as the oligos described below.
OUR IMMUNE SELF AND IMMUNOTHERAPY
Quite aside from the ageing process that makes us
different with every passing day, we are also continuously
shaped by our environment. To survive our body needs
specialist cells that act as expert agents to recognise friend
Figure 3. Tree of life.
From the new insights into our immunological system,
Behring’s first serum therapy, or antibody therapy, against
diphtheria has now expanded into a whole host of
immunotherapies, not only against microorganisms but
also against cells that have become renegade as cancer
cells , and self-molecules that are misrecognised by our
immune system as foreign, and molecules that cause
atherosclerosis.
The nature of targeting
Drug targeting or drug delivery has been on the minds
of drug developers ever since Ehrlich proposed his magic
bullet theory of drug action (18). His approach was
@Real Academia Nacional de Farmacia. Spain
from foe, and for this we have evolved an exquisitely
effective immunological surveillance system over
evolutionary time: An immediate response innate system
that recognises enemies met over evolutionary time, and
an adaptive system that remoulds itself quickly to
recognise new enemies both from within (e.g. in the form
of cancer cells), and from outside, in the form of new
microorganisms and new aggressive variants of old
organisms (e.g. Zika and Ebola viruses, and new strains of
influenza viruses). Cancer can be regarded as a failure of
the immune system. Our resident microorganisms (our
microbiome; Figure 3) participate more closely in our
immunological remoulding than we thought even as
recently as two decades ago (16,17).
structural modification of a lead compound to optimise the
benefit-harm balance. Salvarsan his first magic bullet was
compound 606 in the series he screened. This approach to
drug screening is still current and has found new life in the
repurposing of existing drugs. The second major approach
to optimising drug delivery was through the development
of sophisticated dosage forms such as osmotic pumps,
transdermal patches. Depot injections, and liposomal
systems. Both approaches contributed albeit modestly to
the march of medicine towards better therapies.
With the unravelling of the double-helical structure of
DNA and detailed understanding of the expression of
genes to functional proteins, drug developers began to
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