RNA - Genetherapys
Spoke 6 - RNA Drug Development


RNA-based technologies are emerging as disruptive therapeutic options, as small biotech companies and academic groups can rapidly develop RNA-based drugs to manipulate gene expression by synthetic mRNAs or to specifically target mRNAs for previously undruggable proteins and non-coding RNAs by RNA-interference and antisense oligonucleotides (ASOs).
Facing several obstacles for the therapeutic application of these technologies, researchers lack a complete understanding of the regulatory circuits operating on RNA metabolism. Other concern include knowing the effects of post-transcriptional modifications and RNA folding on the interaction with therapeutic molecules, off-target effects, unproductive uptake of ASOs and the tendency of ASOs to sequester RNA binding proteins in unproductive complexes.

Spoke 6 addresses these hurdles with three complementary Work Packages (WPs), which focus is on non-coding RNAs: miRNAs, lncRNAs, circRNAs and introns.

WP 6.1Technological Approaches for RNA Therapeutics, aims to provide a multimodal and multitarget approach to RNA therapeutics by the sequencing, imaging, and editing of RNAs coupled with a tailored computational and artificial intelligence approaches.

WP 6.1 oversees three main tasks:

  • developing programmable RNA editing protocols (UniBa, IFC-CNR and IIT)
  • implementing native RNA sequencing technology (IIT)
  • developing an optical microscopy platform (IIT)

WP 6.2Development of RNA-based and RNA-targeting compounds for therapeutic uses. WP 6.2 aims to design, select and characterize compounds with ‘beyond-state-of-the art’ properties in terms of selectivity, in vivo resistance, binding strength to the target, and control by external. The WP also focuses on optimizing a platform for mRNA therapeutics.
WP 6.2 oversees three main tasks:

  • developing new RNA-targeting compounds (UniPD, UniBo, IC-CNR)
  • setting fluorogenic / modulable RNA aptamers and synthetic DNA/RNA nanoscaffolds (IBB-CNR, IEOS-CNR, UniNA, UniSi,UniRoma2)
  • creating new and more efficient methodology for the synthesis and formulation of chemically modified mRNAs (UniNa, UniPD)
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WP 6.3 – Test-cases and identification of novel therapeutic RNA molecules.
WP 6.3 oversees four main tasks:

  • developing approaches for ncRNA restoration toward the development of innovative RNA-based therapies (UniPD, IBF-CNR)
  • developing specific targeted approaches for oncogenic lncRNAs and circRNAs (IGB-CNR, UniPD )
  • locating ASO targeting telomere dysfunction-induced ncRNA to treat human telomere-driven diseases: (IGM-CNR)
  • developing of computational and experimental pipelines and innovative ASO to target alternative splicing (IGM-CNR, RiMed)
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