A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown

© 2019 Elsevier Inc. Gene knockdown is an advantageous therapeutic strategy to lower dangerous genetic over-expression. However, the molecules responsible for initiating this process are unstable. Porous nanoparticles called metal-organic frameworks can encapsulate, protect, and deliver these compounds efficaciously without the need for chemical modifications—commonly done to enhance stability. By applying this platform technology, this work demonstrates the successful reduction in expression of a gene by avoiding retention and subsequent degradation in cellular compartments.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (NanoMOFdeli), ERC-2016-COG 726380, and (SUPUVIR) no. 722380. M.H.T. thanks the Gates Cambridge Trust for funding, S. Haddad for helpful discussions, and A. Li for assistance with data visualization. D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. S.B.d.Q.F., F.M.R., and D.I.J. were funded by Cancer Research UK Senior Group Leader Grant CRUK/A15678. O.K.F. gratefully acknowledges DTRA for financial support (grant HDTRA-1-14-1-0014). C.F.K. acknowledges funding from the UK Engineering and Physical Sciences Research Council (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research Council (grants MR/K015850/1 and MR/K02292X/1), and Infinitus (China) Ltd. Computational work was supported by the Cambridge High Performance Computing Cluster, Darwin