Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations

Abstract Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis. Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as an alt...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jocelyn Loo, Ian Sicher, Ailin Goff, Ockchul Kim, Nicole Clary, Alexander Alexeev, Todd Sulchek, Alla Zamarayeva, Sewoon Han, Miguel Calero-Garcia
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3c1817175ef14e56ba195de35e1cb00e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3c1817175ef14e56ba195de35e1cb00e
record_format	dspace
spelling	oai:doaj.org-article:3c1817175ef14e56ba195de35e1cb00e2021-11-08T10:50:38ZMicrofluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations10.1038/s41598-021-00893-42045-2322https://doaj.org/article/3c1817175ef14e56ba195de35e1cb00e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00893-4https://doaj.org/toc/2045-2322Abstract Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis. Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as an alternative to enzyme replacement therapies, and to express chimeric antigen receptors (CARs) on immune cells for the treatment of cancer. We designed a novel microfluidic device that allows for efficient mRNA delivery via volume exchange for convective transfection (VECT). In the device, cells flow through a ridged channel that enforces a series of ultra-fast and large intensity deformations able to transiently open pores and induce convective transport of mRNA into the cell. Here, we describe efficient delivery of mRNA into T cells, natural killer (NK) cells and hematopoietic stem and progenitor cells (HSPCs), three human primary cell types widely used for ex vivo gene therapy applications. Results demonstrate that the device can operate at a wide range of cell and payload concentrations and that ultra-fast compressions do not have a negative impact on T cell function, making this a novel and competitive platform for the development of ex vivo mRNA-based gene therapies and other cell products engineered with mRNA.Jocelyn LooIan SicherAilin GoffOckchul KimNicole ClaryAlexander AlexeevTodd SulchekAlla ZamarayevaSewoon HanMiguel Calero-GarciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jocelyn Loo Ian Sicher Ailin Goff Ockchul Kim Nicole Clary Alexander Alexeev Todd Sulchek Alla Zamarayeva Sewoon Han Miguel Calero-Garcia Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
description	Abstract Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis. Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as an alternative to enzyme replacement therapies, and to express chimeric antigen receptors (CARs) on immune cells for the treatment of cancer. We designed a novel microfluidic device that allows for efficient mRNA delivery via volume exchange for convective transfection (VECT). In the device, cells flow through a ridged channel that enforces a series of ultra-fast and large intensity deformations able to transiently open pores and induce convective transport of mRNA into the cell. Here, we describe efficient delivery of mRNA into T cells, natural killer (NK) cells and hematopoietic stem and progenitor cells (HSPCs), three human primary cell types widely used for ex vivo gene therapy applications. Results demonstrate that the device can operate at a wide range of cell and payload concentrations and that ultra-fast compressions do not have a negative impact on T cell function, making this a novel and competitive platform for the development of ex vivo mRNA-based gene therapies and other cell products engineered with mRNA.
format	article
author	Jocelyn Loo Ian Sicher Ailin Goff Ockchul Kim Nicole Clary Alexander Alexeev Todd Sulchek Alla Zamarayeva Sewoon Han Miguel Calero-Garcia
author_facet	Jocelyn Loo Ian Sicher Ailin Goff Ockchul Kim Nicole Clary Alexander Alexeev Todd Sulchek Alla Zamarayeva Sewoon Han Miguel Calero-Garcia
author_sort	Jocelyn Loo
title	Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
title_short	Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
title_full	Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
title_fullStr	Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
title_full_unstemmed	Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
title_sort	microfluidic transfection of mrna into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3c1817175ef14e56ba195de35e1cb00e
work_keys_str_mv	AT jocelynloo microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT iansicher microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT ailingoff microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT ockchulkim microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT nicoleclary microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT alexanderalexeev microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT toddsulchek microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT allazamarayeva microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT sewoonhan microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations AT miguelcalerogarcia microfluidictransfectionofmrnaintohumanprimarylymphocytesandhematopoieticstemandprogenitorcellsusingultrafastphysicaldeformations
_version_	1718442609782816768

Microfluidic transfection of mRNA into human primary lymphocytes and hematopoietic stem and progenitor cells using ultra-fast physical deformations

Ejemplares similares