SynDesign

SynDesign designs and evaluates prime editing guide RNAs (pegRNAs) for saturation genome editing (SGE), enabling systematic generation of all single-nucleotide variants (SNVs) in coding regions for functional assessment.

Key Features:

• Automated PegRNA Design: Generates feasible pegRNA designs for specified target genes or variants using automated algorithms.
• Saturation Genome Editing Design: Produces designs to generate all possible SNVs within a coding region for SGE experiments.
• Efficiency Prediction Models: Applies predictive models including DeepPrime and DeepPrime-FT to estimate prime editing efficiencies across prime editors and cell types.
• Synonymous Mutation Markers: Incorporates synonymous mutation markers into top-scoring designs to modulate mismatch repair and provide sequencing-identifiable markers for deep sequencing analysis.
• Library Construction Integration: Outputs pegRNA designs formatted for construction of precision pegRNA libraries for functional evaluation studies.
• Curated Design Outputs: Produces a curated list of pegRNA designs prioritized for experimental validation.

Scientific Applications:

• Functional characterization of disease-associated variants: Enables systematic assessment of variant effects on gene function using SGE-generated SNV libraries.
• Variant effect mapping: Supports comprehensive generation and evaluation of all coding-region SNVs to map sequence-to-function relationships.
• Target discovery and therapeutic research: Facilitates identification of potential therapeutic targets and variant impact relevant to personalized medicine through large-scale functional screens.

Methodology:

Users specify a target gene or variant; the tool automatically generates feasible pegRNA designs using advanced algorithms; predictive models (DeepPrime/DeepPrime-FT) assess editing efficiency for different prime editors and cell types; top-scoring designs are enhanced with synonymous mutation markers; a curated list of pegRNA designs is produced for experimental validation.