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

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Bulgaria

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.139

RIV identification code

RIV/00216224:14740/21:00119670

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.33549/physiolres.934571

UT WoS

000675528500016

Keywords in English

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

Abstract

V originále

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

Citovat

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://dx.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 = {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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