First-in-Humans Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement
Deaconess Hospital · Memorial Sloan Kettering Cancer Center · +8 more institutions
Abstract
UNLABELLED: RNA interference (RNAi) is a potent and specific mechanism for regulating gene expression. Harnessing RNAi to silence genes involved in disease holds promise for the development of a new class of therapeutics. Delivery is key to realizing the potential of RNAi, and lipid nanoparticles (LNP) have proved effective in delivery of siRNAs to the liver and to tumors in animals. To examine the activity and safety of LNP-formulated siRNAs in humans, we initiated a trial of ALN-VSP, an LNP formulation of siRNAs targeting VEGF and kinesin spindle protein (KSP), in patients with cancer. Here, we show detection of drug in tumor biopsies, siRNA-mediated mRNA cleavage in the liver, pharmacodynamics suggestive of…
Citation impact
- FWCI
- 38.73
- Percentile
- 100%
- References
- 49
Authors
28- JTJosep TaberneroCorresponding
Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Alnylam Pharmaceuticals (United States), Universitat de València, Hadassah Medical Center, The Barbara Ann Karmanos Cancer Institute, Sarah Cannon, Dana-Farber Cancer Institute, Hospital Universitario Virgen del Rocío, INCLIVA Health Research Institute
- GIGeoffrey I. Shapiro
Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Alnylam Pharmaceuticals (United States), Universitat de València, Hadassah Medical Center, The Barbara Ann Karmanos Cancer Institute, Sarah Cannon, Dana-Farber Cancer Institute, Hospital Universitario Virgen del Rocío, INCLIVA Health Research Institute
- PLPatricia LoRusso
Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Alnylam Pharmaceuticals (United States), Universitat de València, Hadassah Medical Center, The Barbara Ann Karmanos Cancer Institute, Sarah Cannon, Dana-Farber Cancer Institute, Hospital Universitario Virgen del Rocío, INCLIVA Health Research Institute
- ACAndrés Cervantes
Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Alnylam Pharmaceuticals (United States), Universitat de València, Hadassah Medical Center, The Barbara Ann Karmanos Cancer Institute, Sarah Cannon, Dana-Farber Cancer Institute, Hospital Universitario Virgen del Rocío, INCLIVA Health Research Institute
- GKGary K. Schwartz
Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Alnylam Pharmaceuticals (United States), Universitat de València, Hadassah Medical Center, The Barbara Ann Karmanos Cancer Institute, Sarah Cannon, Dana-Farber Cancer Institute, Hospital Universitario Virgen del Rocío, INCLIVA Health Research Institute
Topics & keywords
- RNA interference
- Small interfering RNA
- Cancer
- Cancer research
- Druggability
- Biology
- Medicine
- Bioinformatics
- Good health and well-being