TY - JOUR
T1 - A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown
AU - Teplensky, Michelle H.
AU - Fantham, Marcus
AU - Poudel, Chetan
AU - Hockings, Colin
AU - Lu, Meng
AU - Guna, Alina
AU - Aragones-Anglada, Marta
AU - Moghadam, Peyman Z.
AU - Li, Peng
AU - Farha, Omar K.
AU - Bernaldo de Quirós Fernández, Sandra
AU - Richards, Frances M.
AU - Jodrell, Duncan I.
AU - Kaminski Schierle, Gabriele
AU - Kaminski, Clemens F.
AU - Fairen-Jimenez, David
N1 - Funding Information:
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.
Funding Information:
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. Conceptualization, M.H.T. and D.F.-J.; Methodology, M.H.T. and D.F.-J.; Investigation, M.H.T. M.F. C.P. C.H. M.L. A.G. and P.L.; Software, M.A.-A. and P.Z.M.; Writing ? Original Draft, M.H.T. and D.F.-J.; Writing ? Review & Editing, M.H.T. M.F. C.P. C.H. M.L. A.G. M.A.-A. P.Z.M. P.L. O.K.F. S.B.d.Q.F. F.M.R. D.I.J. G.K.S. C.F.K. and D.F.-J.; Supervision, O.K.F. S.B.d.Q.F. F.M.R. D.I.J. G.K.S. C.F.K. and D.F.-J.; Project Administration and Funding Acquisition, D.F.-J. D.F.-J. is a founder of Immaterial Labs and a member of its scientific advisory board; P.Z.M. is a consultant for Immaterial Labs. O.K.F. is a founder of NuMat and a member of its scientific advisory board. All the other authors declare no other competing interests. M.H.T. C.H. G.K.S. and D.F.-J. have filed a patent related to this work.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11/14
Y1 - 2019/11/14
N2 - 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.
AB - 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.
KW - SDG3: Good health and well-being
KW - adsorption
KW - cancer
KW - drug delivery
KW - endosomal escape
KW - gene knockdown
KW - gene knockdown
KW - metal-organic frameworks
KW - molecular simulation
KW - structured illumination microscopy
UR - http://www.scopus.com/inward/record.url?scp=85074750545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074750545&partnerID=8YFLogxK
U2 - 10.1016/j.chempr.2019.08.015
DO - 10.1016/j.chempr.2019.08.015
M3 - Article
AN - SCOPUS:85074750545
VL - 5
SP - 2926
EP - 2941
JO - Chem
JF - Chem
SN - 2451-9294
IS - 11
ER -
