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Preclinical and clinical development of siRNA-based therapeutics
#MMPMID25666164
Ozcan G
; Ozpolat B
; Coleman RL
; Sood AK
; Lopez-Berestein G
Adv Drug Deliv Rev
2015[Jun]; 87
(?): 108-19
PMID25666164
show ga
The discovery of RNA interference, first in plants and Caenorhabditis elegans and
later in mammalian cells, led to the emergence of a transformative view in
biomedical research. Knowledge of the multiple actions of non-coding RNAs has
truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs
(siRNAs) can be used as tools to study single gene function both in vitro and in
vivo and are an attractive new class of therapeutics, especially against
undruggable targets for the treatment of cancer and other diseases. Despite the
potential of siRNAs in cancer therapy, many challenges remain, including rapid
degradation, poor cellular uptake and off-target effects. Rational design
strategies, selection algorithms, chemical modifications and nanocarriers offer
significant opportunities to overcome these challenges. Here, we review the
development of siRNAs as therapeutic agents from early design to clinical trial,
with special emphasis on the development of EphA2-targeting siRNAs for ovarian
cancer treatment.
|Animals
[MESH]
|Clinical Trials as Topic
[MESH]
|Drug Carriers/chemistry
[MESH]
|Drug Design
[MESH]
|Drug Evaluation, Preclinical
[MESH]
|Female
[MESH]
|Gene Targeting
[MESH]
|Humans
[MESH]
|Nanoparticles/chemistry
[MESH]
|Ovarian Neoplasms/*drug therapy/genetics
[MESH]
|RNA Interference/*drug effects
[MESH]
|RNA, Small Interfering/administration & dosage/adverse
effects/pharmacokinetics/*therapeutic use
[MESH]
free
free
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