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@article{1836836,
author = {Macháčková, Táňa and Vychytilová, Petra and Součková, Kamila and Laga, Richard and Androvic, Ladislav and Mixova, Gabriela and Slabý, Ondřej},
article_location = {Praha},
article_number = {3},
doi = {http://dx.doi.org/10.33549/physiolres.934571},
keywords = {miRNA; miR-215-5p; Animal model; Systemic delivery},
language = {eng},
issn = {0862-8408},
journal = {Physiological research},
title = {Barriers in Systemic Delivery and Preclinical Testing of Synthetic microRNAs in Animal Models: an Experimental Study on miR-215-5p Mimic},
url = {https://www.biomed.cas.cz/physiolres/pdf/2021/70_481.pdf},
volume = {70},
year = {2021}
}
TY - JOUR
ID - 1836836
AU - Macháčková, Táňa - Vychytilová, Petra - Součková, Kamila - Laga, Richard - Androvic, Ladislav - Mixova, Gabriela - Slabý, Ondřej
PY - 2021
TI - Barriers in Systemic Delivery and Preclinical Testing of Synthetic microRNAs in Animal Models: an Experimental Study on miR-215-5p Mimic
JF - Physiological research
VL - 70
IS - 3
SP - 481-487
EP - 481-487
PB - Fyziologický ústav AV ČR
SN - 08628408
KW - miRNA
KW - miR-215-5p
KW - Animal model
KW - Systemic delivery
UR - https://www.biomed.cas.cz/physiolres/pdf/2021/70_481.pdf
N2 - Mus musculus is the most commonly used animal model in microRNA research; however, little is known about the endogenous miRNome of the animals used in the miRNA-targeting preclinical studies with the human xenografts. In the presented study, we evaluated the NOD/SCID gamma mouse model for the preclinical study of systemic miR-215-5p substitution with a semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]-based carrier conjugated with miR-215-5pmimic via a reductively degradable disulfide bond. Murine mmu-miR-215-5p and human hsa-miR-215-5p have a high homology of mature sequences with only one nucleotide substitution. Due to the high homology of hsa-miR-215-5p and mmu-hsa-miR-2155p, a similar expression in human and NOD/SCID gamma mice was expected. Expression of mmu-miR-215 in murine organs did not indicate tissue-specific expression and was highly expressed in all examined tissues. All animals included in the study showed a significantly higher concentration of miR-215-5p in the blood plasma compared to human blood plasma, where miR-215-5p is on the verge of a reliable detection limit. However, circulating mmu-miR-215-5p did not enter the human xenograft tumors generated with colorectal cancer cell lines since the levels of miR-215-5p in control tumors remained notably lower compared to those originally transfected with miR-215-5p. Finally, the systemic administration of polymer-miR-215-5p-mimic conjugate to the tail vein did not increase miR-215-5p in NOD/SCID gamma mouse blood plasma, organs, and subcutaneous tumors. It was impossible to distinguish hsa-miR-215-5p and mmu-miR-215-5p in the murine blood and organs due to the high expression of endogenous mmu-miR-215-5p. In conclusion, the examination of endogenous tissue and circulating miRNome of an experimental animal model of choice might be necessary for future miRNA studies focused on the systemic delivery of miRNA-based drugs conducted in the animal models.
ER -
MACHÁČKOVÁ, Táňa, Petra VYCHYTILOVÁ, Kamila SOUČKOVÁ, Richard LAGA, Ladislav ANDROVIC, Gabriela MIXOVA and Ondřej SLABÝ. Barriers in Systemic Delivery and Preclinical Testing of Synthetic microRNAs in Animal Models: an Experimental Study on miR-215-5p Mimic. \textit{Physiological research}. Praha: Fyziologický ústav AV ČR, 2021, vol.~70, No~3, p.~481-487. ISSN~0862-8408. Available from: https://dx.doi.org/10.33549/physiolres.934571.
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