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

Investor logo

Warning

This publication doesn't include Faculty of Arts. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

MACHÁČKOVÁ Táňa VYCHYTILOVÁ Petra SOUČKOVÁ Kamila LAGA Richard ANDROVIC Ladislav MIXOVA Gabriela SLABÝ Ondřej

Year of publication 2021
Type Article in Periodical
Magazine / Source Physiological research
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.biomed.cas.cz/physiolres/pdf/2021/70_481.pdf
Doi http://dx.doi.org/10.33549/physiolres.934571
Keywords miRNA; miR-215-5p; Animal model; Systemic delivery
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.