State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery

Martijn J.W. Evers, Jayesh A. Kulkarni, Roy van der Meel, Pieter R. Cullis, Pieter Vader, Raymond M. Schiffelers (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenAcademicpeer review

Uittreksel

Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, hampering the ability to reach the cytoplasm of target cells when administered intravenously. As a result, the therapeutic use of siRNA is crucially dependent on delivery strategies. LNPs can encapsulate siRNA to protect it from degradative endonucleases in the circulation, prevent kidney clearance, and provide a vehicle to deliver siRNA in the cell and induce its subsequent release into the cytoplasm. Here, the structure and composition of LNP–siRNA are described including how these affect their pharmacokinetic parameters and gene‐silencing activity. In addition, the evolution of LNP–siRNA production methods is discussed, as the development of rapid‐mixing platforms for the reproducible and scalable manufacturing has facilitated entry of LNP–siRNA into the clinic over the last decade. Finally, the potential of LNPs in delivering other nucleic acids, such as messenger RNA and CRISPR/Cas9 components, is highlighted alongside how a design‐of‐experiment approach may be used to improve the efficacy of LNP formulations.
TaalEngels
Artikelnummer1700375
Aantal pagina's20
TijdschriftSmall Methods
Volume2
Nummer van het tijdschrift9
DOI's
StatusGepubliceerd - 26 apr 2018
Extern gepubliceerdJa

Vingerafdruk

Nanoparticles
Nucleic Acids
Small Interfering RNA
Lipids
Cytoplasm
Clustered Regularly Interspaced Short Palindromic Repeats
Renal Circulation
Endonucleases
Gene Silencing
Therapeutic Uses
Pharmacokinetics
Messenger RNA

Citeer dit

Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M. (2018). State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery. Small Methods, 2(9), [1700375]. DOI: 10.1002/smtd.201700375
Evers, Martijn J.W. ; Kulkarni, Jayesh A. ; van der Meel, Roy ; Cullis, Pieter R. ; Vader, Pieter ; Schiffelers, Raymond M./ State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery. In: Small Methods. 2018 ; Vol. 2, Nr. 9.
@article{1dee47efa2a7433ba4e1444287a76717,
title = "State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery",
abstract = "Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, hampering the ability to reach the cytoplasm of target cells when administered intravenously. As a result, the therapeutic use of siRNA is crucially dependent on delivery strategies. LNPs can encapsulate siRNA to protect it from degradative endonucleases in the circulation, prevent kidney clearance, and provide a vehicle to deliver siRNA in the cell and induce its subsequent release into the cytoplasm. Here, the structure and composition of LNP–siRNA are described including how these affect their pharmacokinetic parameters and gene‐silencing activity. In addition, the evolution of LNP–siRNA production methods is discussed, as the development of rapid‐mixing platforms for the reproducible and scalable manufacturing has facilitated entry of LNP–siRNA into the clinic over the last decade. Finally, the potential of LNPs in delivering other nucleic acids, such as messenger RNA and CRISPR/Cas9 components, is highlighted alongside how a design‐of‐experiment approach may be used to improve the efficacy of LNP formulations.",
author = "Evers, {Martijn J.W.} and Kulkarni, {Jayesh A.} and {van der Meel}, Roy and Cullis, {Pieter R.} and Pieter Vader and Schiffelers, {Raymond M.}",
year = "2018",
month = "4",
day = "26",
doi = "10.1002/smtd.201700375",
language = "English",
volume = "2",
journal = "Small Methods",
issn = "2366-9608",
publisher = "Wiley",
number = "9",

}

State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery. / Evers, Martijn J.W.; Kulkarni, Jayesh A.; van der Meel, Roy; Cullis, Pieter R.; Vader, Pieter; Schiffelers, Raymond M. (Corresponding author).

In: Small Methods, Vol. 2, Nr. 9, 1700375, 26.04.2018.

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenAcademicpeer review

TY - JOUR

T1 - State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery

AU - Evers,Martijn J.W.

AU - Kulkarni,Jayesh A.

AU - van der Meel,Roy

AU - Cullis,Pieter R.

AU - Vader,Pieter

AU - Schiffelers,Raymond M.

PY - 2018/4/26

Y1 - 2018/4/26

N2 - Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, hampering the ability to reach the cytoplasm of target cells when administered intravenously. As a result, the therapeutic use of siRNA is crucially dependent on delivery strategies. LNPs can encapsulate siRNA to protect it from degradative endonucleases in the circulation, prevent kidney clearance, and provide a vehicle to deliver siRNA in the cell and induce its subsequent release into the cytoplasm. Here, the structure and composition of LNP–siRNA are described including how these affect their pharmacokinetic parameters and gene‐silencing activity. In addition, the evolution of LNP–siRNA production methods is discussed, as the development of rapid‐mixing platforms for the reproducible and scalable manufacturing has facilitated entry of LNP–siRNA into the clinic over the last decade. Finally, the potential of LNPs in delivering other nucleic acids, such as messenger RNA and CRISPR/Cas9 components, is highlighted alongside how a design‐of‐experiment approach may be used to improve the efficacy of LNP formulations.

AB - Lipid nanoparticles (LNPs) are currently the most clinically advanced nonviral carriers for the delivery of small interfering RNA (siRNA). Free siRNA molecules suffer from unfavorable physicochemical characteristics and rapid clearance mechanisms, hampering the ability to reach the cytoplasm of target cells when administered intravenously. As a result, the therapeutic use of siRNA is crucially dependent on delivery strategies. LNPs can encapsulate siRNA to protect it from degradative endonucleases in the circulation, prevent kidney clearance, and provide a vehicle to deliver siRNA in the cell and induce its subsequent release into the cytoplasm. Here, the structure and composition of LNP–siRNA are described including how these affect their pharmacokinetic parameters and gene‐silencing activity. In addition, the evolution of LNP–siRNA production methods is discussed, as the development of rapid‐mixing platforms for the reproducible and scalable manufacturing has facilitated entry of LNP–siRNA into the clinic over the last decade. Finally, the potential of LNPs in delivering other nucleic acids, such as messenger RNA and CRISPR/Cas9 components, is highlighted alongside how a design‐of‐experiment approach may be used to improve the efficacy of LNP formulations.

U2 - 10.1002/smtd.201700375

DO - 10.1002/smtd.201700375

M3 - Review article

VL - 2

JO - Small Methods

T2 - Small Methods

JF - Small Methods

SN - 2366-9608

IS - 9

M1 - 1700375

ER -

Evers MJW, Kulkarni JA, van der Meel R, Cullis PR, Vader P, Schiffelers RM. State‐of‐the‐art design and rapid‐mixing production techniques of lipid nanoparticles for nucleic acid delivery. Small Methods. 2018 apr 26;2(9). 1700375. Beschikbaar vanaf, DOI: 10.1002/smtd.201700375