Abstract: Systems and methods for predicting deamination efficiency or specificity are provided herein. Information, including a nucleic acid sequence for a gRNA that hybridizes to a target mRNA or structural features of a gRNA-target mRNA scaffold, is input into a model. The model outputs metrics for efficiency or specificity of deamination of a target nucleotide position in a first and/or second mRNA transcribed from a corresponding first and/or second gene. Also provided herein are systems and methods of using a model that includes a first portion and a second portion, where the first portion includes an attention mechanism. Also provided herein are systems and methods for generating a candidate sequence for a gRNA using, as input to a model, seed information including a seed gRNA nucleic acid sequence and a target mRNA nucleic acid sequence.

Abstract: Systems and methods for predicting deamination efficiency or specificity associated with a guide RNA (gRNA) are provided. A nucleic acid sequence for the gRNA is received. Responsive to inputting a data structure into a model, a metric for an efficiency or specificity of deamination by a first Adenosine Deaminase Acting on RNA (ADAR) protein of a target nucleotide position in mRNA transcribed from a target gene is obtained as output from the model. The data structure includes an encoding of the nucleic acid sequence for the gRNA.

Abstract: Disclosed herein are engineered RNAs and compositions comprising the same for treatment of diseases or conditions in a subject. Also disclosed herein are methods of treating diseases or conditions in a subject by administering engineered RNAs, polynucleotides encoding the described engineered RNAs, or pharmaceutical compositions described here.

Abstract: Provided herein are engineered guides configured, upon hybridization to target RNA molecules, to form double stranded RNA substrates comprising (i) a region comprising at least one structural feature; and (ii) a first internal loop and a second internal loop, wherein the double stranded RNA substrates recruit RNA editing entities and facilitate chemical modifications of base nucleotides in the target RNA molecules. Also provided herein are compositions, vectors, and cells comprising the engineered guides disclosed herein. Also provided herein are methods of introducing the engineered guides described herein into cells and methods of treating a disease or condition in a subject in need thereof comprising administering to the subject the engineered guides, polynucleotides encoding the engineered guides, delivery vehicles comprising such engineered guides or such polynucleotides, or pharmaceutical compositions comprising any one of these as described herein.

Abstract: Disclosed herein are engineered guide RNAs and compositions comprising the same for treatment of diseases or conditions in a subject. Also disclosed herein are methods of treating diseases or conditions in a subject by administering engineered guide RNAs or pharmaceutical compositions described herein.

Abstract: Disclosed herein are engineered guide RNAs and compositions comprising the same for treatment of diseases or conditions in a subject. Also disclosed herein are methods of treating diseases or conditions in a subject by administering engineered guide RNAs or pharmaceutical compositions described herein.