Scalable production of siRNA‐encapsulated extracellular vesicles for the inhibition of KRAS‐mutant cancer using acoustic shock waves

Extracellular vesicles (EVs) have emerged as a potential delivery vehicle for nucleic‐acid‐based therapeutics, but challenges related to their large‐scale production and cargo‐loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel “shock wave extra...

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Bibliographic Details
Published in:Journal of extracellular vesicles 2024-09, Vol.13 (9), p.e12508-n/a
Main Authors: Kim, Hyo Kyeong, Choi, Yujeong, Kim, Kyoung Hwa, Byun, Yeongju, Kim, Tae Hee, Kim, Jae Hwan, An, Shung Hyun, Bae, DaeHo, Choi, Myeong Kwan, Lee, Minyoung, Kang, Gwansuk, Chung, Jihwa, Kim, Seok‐Hyun, Kwon, Kihwan
Format: Article
Language:English
Subjects:
Animals
anti‐cancer effects
bovine‐milk‐derived extracellular vesicles
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - therapy
Cattle
Cell Line, Tumor
Extracellular Vesicles - metabolism
gene delivery
Humans
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - therapy
Mice
Mutation
non‐small cell lung cancer
nucleic‐acid‐based therapeutics
Proto-Oncogene Proteins p21(ras) - genetics
Proto-Oncogene Proteins p21(ras) - metabolism
RNA, Small Interfering - genetics
scalable production
shock wave
siRNA against KRAS G12C mutant
Xenograft Model Antitumor Assays
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Summary:Extracellular vesicles (EVs) have emerged as a potential delivery vehicle for nucleic‐acid‐based therapeutics, but challenges related to their large‐scale production and cargo‐loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel “shock wave extracellular vesicles engineering technology” (SWEET) as a non‐genetic, scalable manufacturing strategy that uses shock waves (SWs) to encapsulate siRNAs in EVs. Here, we describe the use of the SWEET platform to load large quantities of KRASG12C‐targeting siRNA into small bovine‐milk‐derived EVs (sBMEVs), with high efficiency. The siRNA‐loaded sBMEVs effectively silenced oncogenic KRASG12C expression in cancer cells; they inhibited tumour growth when administered intravenously in a non‐small cell lung cancer xenograft mouse model. Our study demonstrates the potential for the SWEET platform to serve as a novel method that allows large‐scale production of cargo‐loaded EVs for use in a wide range of therapeutic applications.
ISSN:2001-3078
2001-3078
DOI:10.1002/jev2.12508