Barriers in Systemic Delivery and Preclinical Testing of
Synthetic microRNAs in Animal Models: an Experimental Study on
miR-215-5p Mimic

J 2021

Barriers in Systemic Delivery and Preclinical Testing of Synthetic microRNAs in Animal Models: an Experimental Study on miR-215-5p Mimic

MACHÁČKOVÁ, Táňa; Petra VYCHYTILOVÁ; Kamila SOUČKOVÁ; Richard LAGA; Ladislav ANDROVIC et. al.

Basic information

Original name

Barriers in Systemic Delivery and Preclinical Testing of Synthetic microRNAs in Animal Models: an Experimental Study on miR-215-5p Mimic

Authors

MACHÁČKOVÁ, Táňa (203 Czech Republic, belonging to the institution); Petra VYCHYTILOVÁ (203 Czech Republic, belonging to the institution); Kamila SOUČKOVÁ (203 Czech Republic, belonging to the institution); Richard LAGA (203 Czech Republic); Ladislav ANDROVIC (203 Czech Republic); Gabriela MIXOVA (203 Czech Republic) and Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Physiological research, Praha, Fyziologický ústav AV ČR, 2021, 0862-8408

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30105 Physiology

Country of publisher

Bulgaria

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 2.139

RIV identification code

RIV/00216224:14740/21:00119670

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.33549/physiolres.934571

UT WoS

000675528500016

EID Scopus

2-s2.0-85112124281

Keywords in English

miRNA; miR-215-5p; Animal model; Systemic delivery

Abstract

In the original language

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.

Links

GA16-18257S, research and development project

Name: Studium mechanizmu spojeného s nádorově supresorovou funkcí miR-215 a substituce této miRNA jako nové lečebné strategie u kolorektálního karcinomu

Investor: Czech Science Foundation

Cite

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. Physiological research. Praha: Fyziologický ústav AV ČR, 2021, vol. 70, No 3, p. 481-487. ISSN 0862-8408. Available from: https://doi.org/10.33549/physiolres.934571.

@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 = {https://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://doi.org/10.33549/physiolres.934571.

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