TY - JOUR
T1 - Strategies, design, and chemistry in siRNA delivery systems
AU - Dong, Yizhou
AU - Siegwart, Daniel J.
AU - Anderson, Daniel G.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/4
Y1 - 2019/4
N2 - Emerging therapeutics that utilize RNA interference (RNAi) have the potential to treat broad classes of diseases due to their ability to reversibly silence target genes. In August 2018, the FDA approved the first siRNA therapeutic, called ONPATTRO™ (Patisiran), for the treatment of transthyretin-mediated amyloidosis. This was an important milestone for the field of siRNA delivery that opens the door for additional siRNA drugs. Currently, >20 small interfering RNA (siRNA)-based therapies are in clinical trials for a wide variety of diseases including cancers, genetic disorders, and viral infections. To maximize therapeutic benefits of siRNA-based drugs, a number of chemical strategies have been applied to address issues associated with efficacy, specificity, and safety. This review focuses on the chemical perspectives behind non-viral siRNA delivery systems, including siRNA synthesis, siRNA conjugates, and nanoparticle delivery using nucleotides, lipids, and polymers. Tracing and understanding the chemical development of strategies to make siRNAs into drugs is important to guide development of additional clinical candidates and enable prolonged success of siRNA therapeutics.
AB - Emerging therapeutics that utilize RNA interference (RNAi) have the potential to treat broad classes of diseases due to their ability to reversibly silence target genes. In August 2018, the FDA approved the first siRNA therapeutic, called ONPATTRO™ (Patisiran), for the treatment of transthyretin-mediated amyloidosis. This was an important milestone for the field of siRNA delivery that opens the door for additional siRNA drugs. Currently, >20 small interfering RNA (siRNA)-based therapies are in clinical trials for a wide variety of diseases including cancers, genetic disorders, and viral infections. To maximize therapeutic benefits of siRNA-based drugs, a number of chemical strategies have been applied to address issues associated with efficacy, specificity, and safety. This review focuses on the chemical perspectives behind non-viral siRNA delivery systems, including siRNA synthesis, siRNA conjugates, and nanoparticle delivery using nucleotides, lipids, and polymers. Tracing and understanding the chemical development of strategies to make siRNAs into drugs is important to guide development of additional clinical candidates and enable prolonged success of siRNA therapeutics.
KW - Nanomaterials
KW - Therapeutics
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=85068778644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068778644&partnerID=8YFLogxK
U2 - 10.1016/j.addr.2019.05.004
DO - 10.1016/j.addr.2019.05.004
M3 - Review article
C2 - 31102606
AN - SCOPUS:85068778644
SN - 0169-409X
VL - 144
SP - 133
EP - 147
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
ER -