MicroRNAs (miRs) are short, non-coding RNA molecules that are able to modify mRNA levels via a short stretch of sequence complementarity. MiRs have been shown to be differentially expressed in osteoarthritic chondrocytes compared to healthy tissue as well as upon dedifferentiation of healthy human articular chondrocytes and multiple chondrocyte-specific mRNA targets of these miRs have been described. My current research involves utilization of the miR targeting mechanism in order to modulate mRNA levels of chondrocyte specific marker genes. To achieve this, I employ DNA editing using CRISPR-Cas9 to modify miR target sequences. Transcripts produced from these modified gene loci can thus be customized to be more or less stable. Ultimately, this approach may open new therapeutic avenues by selectively and specifically tuning the expression levels (and consequently protein levels) of any desired chondrocyte mRNA.
Seidl CI. et al, (2016), Arthritis & rheumatology (hoboken, n.j.), 68, 398 - 409
Lama L. et al, (2014), Transcription, 5
The role of H19-derived miR-675 in human cartilage
Seidl C. et al, (2013), International journal of experimental pathology, 94, A17 - A18
Seidl CI. et al, (2013), Nucleic acids research, 41, 2552 - 2564