RNA-based drug discovery for spinal muscular atrophy: a story of small molecules and antisense oligonucleotides

Torroba, Blanca; Macabuag, Natsuko; Haisma, Elisabeth M; O'Neill, Amy; Herva, María Eugenia; Redis, Roxana S; Templin, Michael V.; Black, Lauren E.; Fischer, David F.

doi:10.1080/17460441.2022.2149733

Cited by 1 publication

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a small molecule drug, Risdiplam, also targets the SMN2 splicing mechanism by enhancing the binding of splice factors, also promoting exon 7 inclusion. Thus, two available therapies targeting mRNA increase full-length SMN2 protein expression through different mechanisms [ 39 ], in order to compensate for the deficit in SMN1 expression.…”

Section: Mutation By Mutation: Asosmentioning

confidence: 99%

What Can RNA-Based Therapy Do for Monogenic Diseases?

Clarke

Amaral

2023

Pharmaceutics

View full text Add to dashboard Cite

The use of RNA-based approaches to treat monogenic diseases (i.e., hereditary disorders caused by mutations in single genes) has been developed on different fronts. One approach uses small antisense oligonucleotides (ASOs) to modulate RNA processing at various stages; namely, to enhance correct splicing, to stimulate exon skipping (to exclude premature termination codon variants), to avoid undesired messenger RNA (mRNA) transcript degradation via the nonsense-mediated decay (NMD) pathway, or to induce mRNA degradation where they encode toxic proteins (e.g., in dominant diseases). Another approach consists in administering mRNA, which, like gene therapy, is a mutation-agnostic approach with potential application to any recessive monogenic disease. This is simpler than gene therapy because instead of requiring targeting of the nucleus, the mRNA only needs to be delivered to the cytoplasm. Although very promising (as demonstrated by COVID-19 vaccines), these approaches still have potential for optimisation, namely regarding delivery efficiency, adverse drug reactions and toxicity.

show abstract

Section: Mutation By Mutation: Asosmentioning

confidence: 99%