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2015 ; 26
(8
): 475-85
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Oligonucleotide Therapies: The Past and the Present
#MMPMID26160334
Lundin KE
; Gissberg O
; Smith CI
Hum Gene Ther
2015[Aug]; 26
(8
): 475-85
PMID26160334
show ga
In this review we address the development of oligonucleotide (ON) medicines from
a historical perspective by listing the landmark discoveries in this field. The
various biological processes that have been targeted and the corresponding ON
interventions found in the literature are discussed together with brief updates
on some of the more recent developments. Most ON therapies act through antisense
mechanisms and are directed against various RNA species, as exemplified by
gapmers, steric block ONs, antagomirs, small interfering RNAs (siRNAs), micro-RNA
mimics, and splice switching ONs. However, ONs binding to Toll-like receptors and
those forming aptamers have completely different modes of action. Similar to
other novel medicines, the path to success has been lined with numerous failures,
where different therapeutic ONs did not stand the test of time. Since the first
ON drug was approved for clinical use in 1998, the therapeutic landscape has
changed considerably, but many challenges remain until the expectations for this
new form of medicine are met. However, there is room for cautious optimism.
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