Nature paper on RGLS4326 | RGLS Message Board Posts

Regulus Therapeutics Inc.

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Msg  561 of 563  at  9/20/2019 8:35:06 AM  by

Dendrimer


Nature paper on RGLS4326

 

Regulus have published their preclinical work on RGLS4326 for ADPKD in Nature. There’s no mention that I could see of the mouse tox that led to the clinical hold. I was interested to note that RGLS4326 uses a mixture of cEt, 2’-F and 2’O-Me modifications.

 

https://www.nature.com/articles/s41467-019-11918-y#Fig6

 

One interesting aspect is the preferential distribution of RGLS4326 to the kidney (8 to 13x the exposure in liver) which I think is unusual for an oligo. If they can figure out why, this would enable a unique kidney targeting capability.

 

I’ve pasted the discussion section below and highlighted the passage that affirms what got me interested in Regulus in the first place - the potential to normalise gene expression in complex diseases.

 

 

 


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