I want to silence a gene with a medical purpose in mind. From what I read, the use of shRNA is frowned upon due to toxicity concerns, with researchers turning instead to artificial miRNA for the development of treatment.

This approach requires the embedding of a shRNA into a miRNA backbone, such as miR-31 or miR-451. Despite I am diving in the literature, I haven't been able to find a clear guide on how to proceed in designing my amiRNA. Could you point me to a resource?

In addition, I am reading that the non-canonical MiR-320 and miR-484 produce RNAs whose 3p is always loaded to AGO, minimizing the off-targets effects due to loading of the passenger strand. I cannot seem to find any example in literature of the -320 or -484 backbone been used to embed a shRNA, is there a reason to this gap?

Thanls