Efficient RNA drug delivery using red blood cell extracellular vesicles

Waqas Muhammad Usman; Tin Chanh Pham; Yuk Yan Kwok; Luyen Tien Vu; Victor Ma; Boya Peng; Yuen San Chan; Likun Wei; Siew Mei Chin; Ajijur Azad; Alex Bai-Liang He; Anskar Y.H. Leung; Mengsu Yang; Ng Shyh-Chang; William C. Cho; Jiahai Shi; Minh T.N. Le

doi:10.1038/s41467-018-04791-8

Efficient RNA drug delivery using red blood cell extracellular vesicles

Waqas Muhammad Usman, Tin Chanh Pham, Yuk Yan Kwok, Luyen Tien Vu, Victor Ma, Boya Peng, Yuen San Chan, Likun Wei, Siew Mei Chin, Ajijur Azad, Alex Bai-Liang He, Anskar Y.H. Leung, Mengsu Yang, Ng Shyh-Chang, William C. Cho, Jiahai Shi, Minh T.N. Le^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

580 Citations (Scopus)

375 Downloads (CityUHK Scholars)

Abstract

Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

Original language	English
Article number	2359 (2018)
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-04791-8
Publication status	Published - 15 Jun 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Publisher's Copyright Statement

Usman, W. M., Pham, T. C., Kwok, Y. Y., Vu, L. T., Ma, V., Peng, B., ... Le, M. T. N. (2018). Efficient RNA drug delivery using red blood cell extracellular vesicles. Nature Communications, 9, [2359 (2018)]. DOI: 10.1038/s41467-018-04791-8. This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

RGC Funding Information

RGC-funded

Access Output

10.1038/s41467-018-04791-8

23928826.pdfFinal Published version, 6.1 MBLicence: CC BY

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

Usman, W. M., Pham, T. C., Kwok, Y. Y., Vu, L. T., Ma, V., Peng, B., Chan, Y. S., Wei, L., Chin, S. M., Azad, A., He, A. B.-L., Leung, A. Y. H., Yang, M., Shyh-Chang, N., Cho, W. C., Shi, J., & Le, M. T. N. (2018). Efficient RNA drug delivery using red blood cell extracellular vesicles. Nature Communications, 9, Article 2359 (2018). https://doi.org/10.1038/s41467-018-04791-8

@article{5690d183e43647799cca1bdb85b3e165,

title = "Efficient RNA drug delivery using red blood cell extracellular vesicles",

abstract = "Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.",

author = "Usman, {Waqas Muhammad} and Pham, {Tin Chanh} and Kwok, {Yuk Yan} and Vu, {Luyen Tien} and Victor Ma and Boya Peng and Chan, {Yuen San} and Likun Wei and Chin, {Siew Mei} and Ajijur Azad and He, {Alex Bai-Liang} and Leung, {Anskar Y.H.} and Mengsu Yang and Ng Shyh-Chang and Cho, {William C.} and Jiahai Shi and Le, {Minh T.N.}",

year = "2018",

month = jun,

day = "15",

doi = "10.1038/s41467-018-04791-8",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer Nature",

}

TY - JOUR

T1 - Efficient RNA drug delivery using red blood cell extracellular vesicles

AU - Usman, Waqas Muhammad

AU - Pham, Tin Chanh

AU - Kwok, Yuk Yan

AU - Vu, Luyen Tien

AU - Ma, Victor

AU - Peng, Boya

AU - Chan, Yuen San

AU - Wei, Likun

AU - Chin, Siew Mei

AU - Azad, Ajijur

AU - He, Alex Bai-Liang

AU - Leung, Anskar Y.H.

AU - Yang, Mengsu

AU - Shyh-Chang, Ng

AU - Cho, William C.

AU - Shi, Jiahai

AU - Le, Minh T.N.

PY - 2018/6/15

Y1 - 2018/6/15

N2 - Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

AB - Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

UR - http://www.scopus.com/inward/record.url?scp=85048721395&partnerID=8YFLogxK

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85048721395&origin=recordpage

U2 - 10.1038/s41467-018-04791-8

DO - 10.1038/s41467-018-04791-8

M3 - RGC 21 - Publication in refereed journal

C2 - 29907766

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 2359 (2018)

ER -

Efficient RNA drug delivery using red blood cell extracellular vesicles

Abstract

UN SDGs

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

ECS: The Role of Tumor-secreted miR-125b in Fibroblast Differentiation during Metastasis

Cite this

Efficient RNA drug delivery using red blood cell extracellular vesicles

Abstract

UN SDGs

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

ECS: The Role of Tumor-secreted miR-125b in Fibroblast Differentiation during Metastasis

Cite this