Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors

Stijn R.J. Hofstraat; Tom Anbergen; Robby Zwolsman; Jeroen Deckers; Yuri van Elsas; Mirre M. Trines; Iris Versteeg; Daniek Hoorn; Gijs W.B. Ros; Branca M. Bartelet; Merel M.A. Hendrikx; Youssef B. Darwish; Teun Kleuskens; Francisca Borges; Rianne J.F. Maas; Lars M. Verhalle; Willem Tielemans; Pieter Vader; Olivier G. de Jong; Tommaso Tabaglio; Dave Keng Boon Wee; Abraham J.P. Teunissen; Eliane Brechbühl; Henk M. Janssen; P. Michel Fransen; Anne de Dreu; David P. Schrijver; Bram Priem; Yohana C. Toner; Thijs J. Beldman; Mihai G. Netea; Willem J.M. Mulder; Ewelina Kluza; Roy van der Meel

doi:10.1038/s41565-024-01847-3

Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors

Stijn R.J. Hofstraat, Tom Anbergen, Robby Zwolsman, Jeroen Deckers, Yuri van Elsas, Mirre M. Trines, Iris Versteeg, Daniek Hoorn, Gijs W.B. Ros, Branca M. Bartelet, Merel M.A. Hendrikx, Youssef B. Darwish, Teun Kleuskens, Francisca Borges, Rianne J.F. Maas, Lars M. Verhalle, Willem Tielemans, Pieter Vader, Olivier G. de Jong, Tommaso TabaglioDave Keng Boon Wee, Abraham J.P. Teunissen, Eliane Brechbühl, Henk M. Janssen, P. Michel Fransen, Anne de Dreu, David P. Schrijver, Bram Priem, Yohana C. Toner, Thijs J. Beldman, Mihai G. Netea, Willem J.M. Mulder^*, Ewelina Kluza, Roy van der Meel^*

^*Corresponding author for this work

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

Abstract

Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein nanoparticle (aNP) that stably incorporates siRNA into its core. We then created a comprehensive library of aNP formulations and extensively characterized their physicochemical properties and in vitro performance. From this library, we selected eight representative aNP-siRNA formulations and evaluated their ability to silence lysosomal-associated membrane protein 1 (Lamp1) expression in immune cell subsets in mice after intravenous administration. Using the most effective aNP identified from the screening process, we tested the platform’s potential for therapeutic gene silencing in a syngeneic murine tumour model. We also demonstrated the aNP platform’s suitability for splice-switching with antisense oligonucleotides and for protein production with messenger RNA by myeloid progenitor cells in the bone marrow. Our data indicate that the aNP platform holds translational potential for delivering various types of nucleic acid therapeutics to myeloid cells and their progenitors.

Original language	English
Pages (from-to)	532–542
Number of pages	11
Journal	Nature nanotechnology
Volume	20
Issue number	4
Early online date	3 Feb 2025
DOIs	https://doi.org/10.1038/s41565-024-01847-3
Publication status	Published - 2025

Access to Document

10.1038/s41565-024-01847-3Licence: CC BY

s41565-024-01847-3Final published version, 4.09 MBLicence: CC BY

Cite this

Hofstraat, S. R. J., Anbergen, T., Zwolsman, R., Deckers, J., van Elsas, Y., Trines, M. M., Versteeg, I., Hoorn, D., Ros, G. W. B., Bartelet, B. M., Hendrikx, M. M. A., Darwish, Y. B., Kleuskens, T., Borges, F., Maas, R. J. F., Verhalle, L. M., Tielemans, W., Vader, P., de Jong, O. G., ... van der Meel, R. (2025). Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors. Nature nanotechnology, 20(4), 532–542. https://doi.org/10.1038/s41565-024-01847-3

@article{7a35c25f6ccb4e2792bf143b8e7bf882,

title = "Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors",

abstract = "Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein nanoparticle (aNP) that stably incorporates siRNA into its core. We then created a comprehensive library of aNP formulations and extensively characterized their physicochemical properties and in vitro performance. From this library, we selected eight representative aNP-siRNA formulations and evaluated their ability to silence lysosomal-associated membrane protein 1 (Lamp1) expression in immune cell subsets in mice after intravenous administration. Using the most effective aNP identified from the screening process, we tested the platform{\textquoteright}s potential for therapeutic gene silencing in a syngeneic murine tumour model. We also demonstrated the aNP platform{\textquoteright}s suitability for splice-switching with antisense oligonucleotides and for protein production with messenger RNA by myeloid progenitor cells in the bone marrow. Our data indicate that the aNP platform holds translational potential for delivering various types of nucleic acid therapeutics to myeloid cells and their progenitors.",

author = "Hofstraat, {Stijn R.J.} and Tom Anbergen and Robby Zwolsman and Jeroen Deckers and {van Elsas}, Yuri and Trines, {Mirre M.} and Iris Versteeg and Daniek Hoorn and Ros, {Gijs W.B.} and Bartelet, {Branca M.} and Hendrikx, {Merel M.A.} and Darwish, {Youssef B.} and Teun Kleuskens and Francisca Borges and Maas, {Rianne J.F.} and Verhalle, {Lars M.} and Willem Tielemans and Pieter Vader and {de Jong}, {Olivier G.} and Tommaso Tabaglio and Wee, {Dave Keng Boon} and Teunissen, {Abraham J.P.} and Eliane Brechb{\"u}hl and Janssen, {Henk M.} and Fransen, {P. Michel} and {de Dreu}, Anne and Schrijver, {David P.} and Bram Priem and Toner, {Yohana C.} and Beldman, {Thijs J.} and Netea, {Mihai G.} and Mulder, {Willem J.M.} and Ewelina Kluza and {van der Meel}, Roy",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

doi = "10.1038/s41565-024-01847-3",

language = "English",

volume = "20",

pages = "532–542",

number = "4",

}

Hofstraat, SRJ, Anbergen, T, Zwolsman, R, Deckers, J, van Elsas, Y, Trines, MM, Versteeg, I, Hoorn, D, Ros, GWB, Bartelet, BM, Hendrikx, MMA, Darwish, YB, Kleuskens, T, Borges, F, Maas, RJF, Verhalle, LM, Tielemans, W, Vader, P, de Jong, OG, Tabaglio, T, Wee, DKB, Teunissen, AJP, Brechbühl, E, Janssen, HM, Fransen, PM, de Dreu, A, Schrijver, DP, Priem, B, Toner, YC, Beldman, TJ, Netea, MG, Mulder, WJM, Kluza, E & van der Meel, R 2025, 'Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors', Nature nanotechnology, vol. 20, no. 4, pp. 532–542. https://doi.org/10.1038/s41565-024-01847-3

TY - JOUR

T1 - Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors

AU - Hofstraat, Stijn R.J.

AU - Anbergen, Tom

AU - Zwolsman, Robby

AU - Deckers, Jeroen

AU - van Elsas, Yuri

AU - Trines, Mirre M.

AU - Versteeg, Iris

AU - Hoorn, Daniek

AU - Ros, Gijs W.B.

AU - Bartelet, Branca M.

AU - Hendrikx, Merel M.A.

AU - Darwish, Youssef B.

AU - Kleuskens, Teun

AU - Borges, Francisca

AU - Maas, Rianne J.F.

AU - Verhalle, Lars M.

AU - Tielemans, Willem

AU - Vader, Pieter

AU - de Jong, Olivier G.

AU - Tabaglio, Tommaso

AU - Wee, Dave Keng Boon

AU - Teunissen, Abraham J.P.

AU - Brechbühl, Eliane

AU - Janssen, Henk M.

AU - Fransen, P. Michel

AU - de Dreu, Anne

AU - Schrijver, David P.

AU - Priem, Bram

AU - Toner, Yohana C.

AU - Beldman, Thijs J.

AU - Netea, Mihai G.

AU - Mulder, Willem J.M.

AU - Kluza, Ewelina

AU - van der Meel, Roy

PY - 2025

Y1 - 2025

N2 - Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein nanoparticle (aNP) that stably incorporates siRNA into its core. We then created a comprehensive library of aNP formulations and extensively characterized their physicochemical properties and in vitro performance. From this library, we selected eight representative aNP-siRNA formulations and evaluated their ability to silence lysosomal-associated membrane protein 1 (Lamp1) expression in immune cell subsets in mice after intravenous administration. Using the most effective aNP identified from the screening process, we tested the platform’s potential for therapeutic gene silencing in a syngeneic murine tumour model. We also demonstrated the aNP platform’s suitability for splice-switching with antisense oligonucleotides and for protein production with messenger RNA by myeloid progenitor cells in the bone marrow. Our data indicate that the aNP platform holds translational potential for delivering various types of nucleic acid therapeutics to myeloid cells and their progenitors.

AB - Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein nanoparticle (aNP) that stably incorporates siRNA into its core. We then created a comprehensive library of aNP formulations and extensively characterized their physicochemical properties and in vitro performance. From this library, we selected eight representative aNP-siRNA formulations and evaluated their ability to silence lysosomal-associated membrane protein 1 (Lamp1) expression in immune cell subsets in mice after intravenous administration. Using the most effective aNP identified from the screening process, we tested the platform’s potential for therapeutic gene silencing in a syngeneic murine tumour model. We also demonstrated the aNP platform’s suitability for splice-switching with antisense oligonucleotides and for protein production with messenger RNA by myeloid progenitor cells in the bone marrow. Our data indicate that the aNP platform holds translational potential for delivering various types of nucleic acid therapeutics to myeloid cells and their progenitors.

UR - http://www.scopus.com/inward/record.url?scp=85218063808&partnerID=8YFLogxK

U2 - 10.1038/s41565-024-01847-3

DO - 10.1038/s41565-024-01847-3

M3 - Article

C2 - 39900620

AN - SCOPUS:85218063808

SN - 1748-3387

VL - 20

SP - 532

EP - 542

JO - Nature nanotechnology

JF - Nature nanotechnology

IS - 4

ER -

Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors

Abstract

Access to Document

Other files and links

Fingerprint

Cite this