Novel rna base editing compositions, systems, methods and uses thereof

The guide RNA of any one of the preceding claims, wherein the guide RNA is bound to a base editor.

The guide RNA of any one of the preceding claims, wherein the guide RNA is bound to an mRNA encoding YAP1 or TAZ.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a region that binds to an ADAR protein.

The guide RNA of any one of the preceding claims, wherein the scaffold is capable of binding RESCUE or REPAIR base editor and directs it to a target site.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a spacer sequence from about 30-36 nucleotides in length.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a spacer sequence of about 30 nucleotides in length.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a mismatch about 17, 24, 25 or 26 nucleotides from the 5′ or 3′ end of the spacer sequence.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a chemical modification at a 5′ terminal nucleotide and/or a 3′ terminal nucleotide of the guide RNA.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises 3× 2′O-methyl and/or phosphorothioate at 5′ and/or 3′ end.

The guide RNA of any one of the preceding claims, wherein the guide RNA comprises a 6 nucleotide extension sequence.

The guide RNA of any one of the preceding claims, wherein the scaffold sequence is derived from Prevotella sp. or Riemerella antaipestifer.

The guide RNA of any one of preceding claims, wherein the scaffold comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95% or greater identity up to 100% identity to any one of SEQ ID NO:

• 5 or 6.

The guide RNA of any one of the preceding claims, wherein the scaffold sequence comprises a Prevotella sp scaffold of SEQ ID NO:

• 5.

An engineered, non-naturally occurring composition for modifying a target RNA base, comprising:

• (a) a scaffold for binding a nucleic acid programmable RNA binding protein, and
• (b) a guide RNA molecule with a spacer sequence having one or more regions complementary to a mRNA encoding a Yes-associated protein 1 (YAP1) or a Transcriptional co-activator with PDZ-binding motif (TAZ or WWTR1).

An engineered, non-naturally occurring composition for modifying a target RNA base, comprising:

• (a) a scaffold for binding a nucleic acid programmable RNA binding protein,
• (b) a base editor, and
• (c) a guide RNA molecule with a spacer sequence having one or more regions complementary to a mRNA encoding Yes-associated protein 1 (YAP1) or Transcriptional co-activator with PDZ-binding motif (TAZ or WWTR1).

The composition of any one of the preceding claims, wherein the modification of targeted mRNA base changes one or more phosphorylation sites of the protein encoded by the target RNA.

The composition of any one of the preceding claims, wherein the target mRNA encodes Transcriptional co-activator with PDZ-binding motif (TAZ) or WWTR1.