PK-modifying anchors significantly alter clearance kinetics, tissue distribution, and efficacy of therapeutics siRNAs

• Main Authors: Bruno M.D.C. Godinho (Author), Emily G. Knox (Author), Samuel Hildebrand (Author), James W. Gilbert (Author), Dimas Echeverria (Author), Zachary Kennedy (Author), Reka A. Haraszti (Author), Chantal M. Ferguson (Author), Andrew H. Coles (Author), Annabelle Biscans (Author), Jillian Caiazzi (Author), Julia F. Alterman (Author), Matthew R. Hassler (Author), Anastasia Khvorova (Author)
• Format: Book
• Published: Elsevier, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Effective systemic delivery of small interfering RNAs (siRNAs) to tissues other than liver remains a challenge. siRNAs are small (∼15 kDa) and therefore rapidly cleared by the kidneys, resulting in limited blood residence times and tissue exposure. Current strategies to improve the unfavorable pharm...