SCIENCE & PLATFORM
Defining Target
Every project starts with a clearly defined biological and translational goal. Together with our partners, we specify indication, organ, cell populations, species, and delivery route, and then design screening strategies and readouts that directly reflect the desired clinical context.
Rational Design
Building on conserved protein–protein interactions, we rationally design short, evolution-inspired peptides and insert them into the AAV capsid. This biases our libraries toward variants with a high probability of achieving cell-type specificity, efficient entry, and the desired trafficking properties.
DNA Barcoding
Within our rAAptr platform, each capsid variant is linked to a unique DNA barcode embedded in the vector genome. After in vivo delivery, barcode expression is quantified by next-generation and single-cell sequencing, enabling high-resolution mapping of capsid performance across tissues and cell types in a single experiment.
Library Screening, Sequencing & Validation
Barcoded capsid libraries are screened in vivo across relevant models and administration routes to enrich variants with the desired tropism and transport behavior. Top candidates are deconvoluted by sequencing and subsequently validated as individual vectors, yielding a focused set of ready-to-develop AAV capsids.
Methodology
rAAVen Therapeutics uses an integrated platform that couples rational peptide design with barcoded AAV libraries and high-throughput sequencing. Within our rAAptr (rational AAV peptide research) platform, each capsid variant is trackable across tissues and cell types, enabling quantitative comparison of tropism and efficacy in a single experiment. This systematic approach allows us to rapidly identify the most promising vectors for a defined indication, organ, and cell population.
Conserved mechanism across species
Our design strategy is grounded in the observation that many receptor–ligand interactions are conserved across mammalian species. By incorporating evolution-inspired peptide motifs into the AAV capsid, rAAVen vectors exploit these conserved pathways to achieve efficient cell entry and high specificity for selected tissue and cell types. Unlike classical directed evolution, the rAAptr platform uses informed design and focused libraries to deliver fast, cost-effective screening with strong cell-type resolution.
Libraries for future
clinical trials
In addition to rationally designed libraries, rAAVen Therapeutics offers large random peptide libraries for broader discovery when target biology is less well defined. These libraries can be profiled in multiple in vivo models—from rodents to non-human primates—and via clinically relevant delivery routes, providing data with high translational value. This enables our partners to build capsid portfolios that are better aligned with future clinical development.
Extended screening and optimization
To further refine selectivity and safety, we also screen promoter and enhancer elements using the same DNA barcoding framework. Regulatory libraries can be evaluated in specific tissues and cell populations to identify combinations of capsid and expression cassette that deliver robust, cell-type–restricted transgene expression. This extended screening supports the design of vectors optimized not only for delivery, but also for precise and controlled gene expression.