Royal College of Surgeons in Ireland
School of Pharmacy and Biomolecular Sciences

Author Of 1 Presentation

Neuroprotection, Regeneration and/or Remyelination Oral Presentation

PS02.05 - Nanomodulation of microRNAs in Macrophages

Presentation Number
Presentation Topic
Neuroprotection, Regeneration and/or Remyelination
Lecture Time
11:09 - 11:21



Multiple Sclerosis (MS) is characterized by central nervous system infiltration of peripheral immune cells, the largest fraction of which are macrophages. The macrophage role in MS is multifaceted, in a pro-inflammatory or ‘M1’ state instructing demyelination and axonal loss, while the anti-inflammatory ‘M2’ state holds a key role in tissue repair and regeneration. Previously, we have identified that IL-10 inhibition of miR-155 is a prominent mechanism utilized by macrophages to maintain an M2 state. Moreover, using a miR-155 floxed x LysMCre model, where miR-155 is specifically deleted from myeloid cells, there was reduced disease onset and less lesion burden in the experimental autoimmune encephalomyelitis (EAE) animal model. Thus, we hypothesize miR-155 inhibition may favorably modulate the macrophage population to an ‘M2’ or pro-repair phenotype, reducing inflammation, alleviating disease progression, mimicking an IL-10 mediated effect.


To investigate the therapeutic potential of a miR-155 anti-miRNA oligonucleotide (AMO) packaged in nanoparticle-based carriers to enhance uptake into macrophages.


4 AMOs were investigated for their ability to inhibit mir-155 in Raw 264.7 and bone marrow-derived macrophages (BMDM). The downstream effect of macrophage pro-inflammatory function in response to mir-155 inhibition was examined by measuring a range of macrophage polarisation parameters, including pro-inflammatory cytokine and nitric oxide (NO) production, expression of M2 markers Arginase-1 and CD206, two markers intricately tied with metabolism in the context of polarisation. PLGA and novel star-shaped polypeptides were also assessed for in vitro macrophage delivery.


A locked nucleic acid (LNA) modified AMO showed the most promising results for mir-155 inhibition in both Raw 264.7 and BMDM. In further studies we show changes in expression of mir-155 target genes that mimic an IL-10 mediated phenotype, while mir-155 independent increases in M2 marker Arginase-1 suggest a more M2 like phenotype. Additionally, star-shaped polypeptides demonstrate the capacity for AMO delivery to BMDM.


mir-155 inhibition can be achieved through delivery of an AMO, and mimics crucial aspects of an IL-10 mediated macrophage phenotype. Star polypeptides represent a promising avenue towards macrophage-specific uptake and future in vivo delivery in MS animal models.