pH sensitive targeting of miR-155 reverses lymphoma oncomiR addiction

Acidity is a general property of tumor environment. The new research in journal Nature described new platform for selective delivery of anti-sense RNAs targeting OncomiR155, a well known target that fuels lymphoma growth.

To this end, the authors attached anti-miR155 RNA sequence to pH sensitive peptide (pHLIP-miR155). In acidic environment, anti-miR155 is cleaved from the peptide and can silence oncomiR155.

In vitro experiments confirmed that pHLIP-miR155 cellular uptake was pH dependent.

The authors showed that pHLIP-miR155 was selectively accumulated in lymphoma tissue and also in kidney. However, the authors did not see any kidney toxicity (see above).

Using spontaneous miR155-driven tumor model, the authors showed that pHLIP-miR155 delivery could improve mice survival, compared to anti-mirR155 alone.

pHLIP-miR155 showed similar anti-tumor effectiveness as mice treated with DOX (in miR155 Tet-Off tumor model) or CHOP (chemotherapy + steroids). Importantly, pHLIP-miR155 did not have toxicity associated with CHOP treatment.

In summary, this approach could be beneficial for treatment of tumors heavily addicted to OncomiRs.

Leave your comments below. Lt me know what do you think about this paper or my analysis.

David Usharauli