TY - JOUR
T1 - Preclinical and clinical development of siRNA-based therapeutics
AU - Ozcan, Gulnihal
AU - Ozpolat, Bulent
AU - Coleman, Robert L.
AU - Sood, Anil K.
AU - Lopez-Berestein, Gabriel
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/6/29
Y1 - 2015/6/29
N2 - 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.
AB - 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.
KW - EphA2
KW - Gene silencing
KW - Nanocarriers
KW - Nanoliposomes
KW - Ovarian cancer
KW - SiRNA
KW - Therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=84937250536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937250536&partnerID=8YFLogxK
U2 - 10.1016/j.addr.2015.01.007
DO - 10.1016/j.addr.2015.01.007
M3 - Review article
C2 - 25666164
AN - SCOPUS:84937250536
SN - 0169-409X
VL - 87
SP - 108
EP - 119
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
ER -