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

Michelle H. Teplensky; Marcus Fantham; Chetan Poudel; Colin Hockings; Meng Lu; Alina Guna; Marta Aragones-Anglada; Peyman Z. Moghadam; Peng Li; Omar K. Farha; Sandra Bernaldo de Quirós Fernández; Frances M. Richards; Duncan I. Jodrell; Gabriele Kaminski Schierle; Clemens F. Kaminski; David Fairen-Jimenez

doi:10.1016/j.chempr.2019.08.015

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

Michelle H. Teplensky, Marcus Fantham, Chetan Poudel, Colin Hockings, Meng Lu, Alina Guna, Marta Aragones-Anglada, Peyman Z. Moghadam, Peng Li, Omar K. Farha, Sandra Bernaldo de Quirós Fernández, Frances M. Richards, Duncan I. Jodrell, Gabriele Kaminski Schierle, Clemens F. Kaminski^*, David Fairen-Jimenez

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2926-2941
Number of pages	16
Journal	Chem
Volume	5
Issue number	11
DOIs	https://doi.org/10.1016/j.chempr.2019.08.015
State	Published - Nov 14 2019

Keywords

SDG3: Good health and well-being
adsorption
cancer
drug delivery
endosomal escape
gene knockdown
gene knockdown
metal-organic frameworks
molecular simulation
structured illumination microscopy

ASJC Scopus subject areas

Chemistry(all)
Biochemistry
Environmental Chemistry
Chemical Engineering(all)
Biochemistry, medical
Materials Chemistry

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Teplensky, M. H., Fantham, M., Poudel, C., Hockings, C., Lu, M., Guna, A., Aragones-Anglada, M., Moghadam, P. Z., Li, P., Farha, O. K., Bernaldo de Quirós Fernández, S., Richards, F. M., Jodrell, D. I., Kaminski Schierle, G., Kaminski, C. F., & Fairen-Jimenez, D. (2019). A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown. Chem, 5(11), 2926-2941. https://doi.org/10.1016/j.chempr.2019.08.015

Teplensky, Michelle H. ; Fantham, Marcus ; Poudel, Chetan ; Hockings, Colin ; Lu, Meng ; Guna, Alina ; Aragones-Anglada, Marta ; Moghadam, Peyman Z. ; Li, Peng ; Farha, Omar K. ; Bernaldo de Quirós Fernández, Sandra ; Richards, Frances M. ; Jodrell, Duncan I. ; Kaminski Schierle, Gabriele ; Kaminski, Clemens F. ; Fairen-Jimenez, David. / A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown. In: Chem. 2019 ; Vol. 5, No. 11. pp. 2926-2941.

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title = "A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown",

abstract = "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.",

keywords = "SDG3: Good health and well-being, adsorption, cancer, drug delivery, endosomal escape, gene knockdown, gene knockdown, metal-organic frameworks, molecular simulation, structured illumination microscopy",

author = "Teplensky, {Michelle H.} and Marcus Fantham and Chetan Poudel and Colin Hockings and Meng Lu and Alina Guna and Marta Aragones-Anglada and Moghadam, {Peyman Z.} and Peng Li and Farha, {Omar K.} and {Bernaldo de Quir{\'o}s Fern{\'a}ndez}, Sandra and Richards, {Frances M.} and Jodrell, {Duncan I.} and {Kaminski Schierle}, Gabriele and Kaminski, {Clemens F.} and David Fairen-Jimenez",

note = "Funding Information: This project has received funding from the European Research Council (ERC) under the European Union{\textquoteright}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. ",

year = "2019",

month = nov,

day = "14",

doi = "10.1016/j.chempr.2019.08.015",

language = "English (US)",

volume = "5",

pages = "2926--2941",

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Teplensky, MH, Fantham, M, Poudel, C, Hockings, C, Lu, M, Guna, A, Aragones-Anglada, M, Moghadam, PZ, Li, P, Farha, OK, Bernaldo de Quirós Fernández, S, Richards, FM, Jodrell, DI, Kaminski Schierle, G, Kaminski, CF & Fairen-Jimenez, D 2019, 'A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown', Chem, vol. 5, no. 11, pp. 2926-2941. https://doi.org/10.1016/j.chempr.2019.08.015

A Highly Porous Metal-Organic Framework System to Deliver Payloads for Gene Knockdown. / Teplensky, Michelle H.; Fantham, Marcus; Poudel, Chetan; Hockings, Colin; Lu, Meng; Guna, Alina; Aragones-Anglada, Marta; Moghadam, Peyman Z.; Li, Peng; Farha, Omar K.; Bernaldo de Quirós Fernández, Sandra; Richards, Frances M.; Jodrell, Duncan I.; Kaminski Schierle, Gabriele; Kaminski, Clemens F.; Fairen-Jimenez, David.

In: Chem, Vol. 5, No. 11, 14.11.2019, p. 2926-2941.

Research output: Contribution to journal › Article › peer-review

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.

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 - metal-organic frameworks

KW - molecular simulation

KW - structured illumination microscopy

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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

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ER -