AAV-rT for Resting T Cells
Directly Targeting Resting T Cells for In Vivo T-Cell Engineering
AAV-rT is a novel engineered AAV capsid developed by AAVnerGene for efficient targeting and transduction of resting T cells. Designed as a delivery platform for in vivo CAR-T and T-cell gene engineering, AAV-rT has the potential to enable direct genetic modification of T cells inside the body without the complex ex vivo manufacturing process required for conventional CAR-T therapy.
Why Target Resting T Cells?
Conventional CAR-T manufacturing requires multiple steps: T-cell collection, activation, ex vivo genetic modification, expansion, quality-control testing, and reinfusion into the patient. This process is complex, time-consuming, and costly.
In contrast, in vivo CAR-T aims to deliver the therapeutic genetic program directly to circulating T cells within the patient.
However, efficient gene delivery to resting, non-activated T cells remains a major challenge. Many commonly used viral vectors show limited efficiency in these cells or require T-cell activation for effective gene transfer.
AAV-rT was developed to address this delivery barrier.
Engineered for Resting T-Cell Targeting
AAV-rT is designed to provide substantially enhanced transduction of resting T cells compared with conventional AAV capsids, creating opportunities for direct in vivo T-cell engineering.
Key Advantages
- Efficient targeting of resting T cells
- Enhanced T-cell transduction compared with conventional AAV capsids
- Potential to eliminate the need for ex vivo T-cell activation and expansion
- Compatible with CAR and other therapeutic gene-expression cassettes
- Potential platform for in vivo gene editing and targeted gene modification
- Enables development of off-the-shelf in vivo T-cell therapies
- AAV-based platform with flexibility for vector and therapeutic-cassette engineering
Enabling In Vivo CAR-T
The traditional CAR-T workflow is:
Patient → T-cell collection → Activation → Ex vivo gene transfer → Expansion → QC → Reinfusion
AAV-rT offers a potential alternative:
AAV-rT + CAR Construct → Direct T-Cell Targeting → In Vivo CAR-T Generation
By moving genetic engineering directly into the patient, an AAV-rT-based approach could potentially simplify CAR-T treatment and reduce manufacturing complexity, treatment time, and cost.
Beyond CAR Expression
AAV-rT can potentially serve as a broader platform for in vivo T-cell engineering, including:
CAR Delivery
Direct delivery of CAR expression cassettes to targeted T-cell populations.
Gene Editing
Delivery of gene-editing components or donor templates for targeted genetic modification.
CAR Knock-In
Potential integration with targeted editing strategies to insert CAR constructs into defined genomic loci.
Targeted Gene Knockout
Combination with gene-editing technologies to disrupt genes that regulate T-cell activity, persistence, exhaustion, or immune function.
Dual-Function T-Cell Engineering
Development of strategies combining CAR introduction with targeted gene modification within a single therapeutic platform.
Potential Applications
AAV-rT may support development of next-generation T-cell therapies for:
- Hematologic malignancies
- Solid tumors
- Autoimmune diseases
- Infectious diseases
- Other indications that could benefit from in vivo immune-cell engineering
Partnership Opportunities
The future of CAR-T may increasingly move from individualized cell manufacturing toward direct in vivo programming of immune cells.
AAVnerGene is open to collaborations with academic and industry partners interested in evaluating AAV-rT for in vivo CAR-T, T-cell gene editing, immune-cell engineering, and other therapeutic applications.
Bring your CAR or gene-editing technology. We provide the T-cell-targeting AAV delivery platform.
