Non-viral in vivo CAR CMC model
In vivo CAR-T programs aim to engineer immune cells directly inside the patient, avoiding the complex vein-to-vein workflow of conventional ex vivo CAR-T manufacturing. Non-viral in vivo CAR approaches typically combine a CAR-encoding nucleic acid payload with a delivery system capable of selective immune-cell targeting, sufficient intracellular delivery, and functional CAR protein expression.
Key CMC questions
For non-viral in vivo CAR programs, three CMC questions are especially critical: whether the payload can drive adequate and durable protein expression, whether the delivery system can achieve a favorable safety and targeting profile, and whether the overall process can be scaled into a reproducible, GMP-ready manufacturing workflow.
Integrated development requirements
In vivo CAR-T is more than a simple RNA-LNP formulation challenge. It requires coordinated development of payload design, targeted delivery strategy, analytical methods, process controls, release strategy, and CMC documentation from early feasibility through IND-enabling development.
CATUG integrated support
CATUG supports in vivo CAR-T development through integrated capabilities in plasmid DNA, RNA drug substance, LNP/tLNP drug product, targeting feasibility, analytical development, GMP manufacturing, and CMC documentation. Beyond conventional mRNA payloads, CATUG has experience with circRNA and other RNA formats, DNA and RNA payload-related workflows, multiple lipid and delivery-system designs, and ongoing internal lipid IP development to support next-generation delivery strategies.
Why CATUG for in vivo CAR
CATUG does not position in vivo CAR-T as a single manufacturing step, but as an integrated CMC workflow. The goal is to help clients evaluate manufacturability early, de-risk payload expression and targeted delivery development, and build a stage-appropriate path toward IND-enabling studies and early clinical translation.
Targeted LNP-enabled in vivo cell therapy model
Targeted LNP-enabled in vivo cell therapy programs extend beyond CAR-T to broader immune-cell and cell-selective engineering applications. These programs rely on tailored delivery systems to transport nucleic acid payloads to specific cell populations in vivo, enabling functional reprogramming without ex vivo cell manipulation. Payload formats may include mRNA, circRNA, saRNA, or DNA/RNA-related strategies depending on the desired expression profile, duration, safety considerations, and mechanism of action.
Key CMC challenges
The core CMC challenges center on payload expression, delivery safety, targeting specificity, ligand selection, conjugation workflow, formulation robustness, analytical characterization, and scalable manufacturing. For non-viral in vivo cell therapy programs, durable and functional protein expression, controlled off-target exposure, and GMP-scalable process design are central to successful translation from feasibility to IND-enabling development.
tLNP engineering strategies
Current tLNP engineering strategies generally include one-pot synthesis, surface conjugation, and post-insertion fusion. One-pot synthesis can simplify the workflow but requires careful ligand-density and formulation control. Surface conjugation offers flexibility for antibody, peptide, or nanobody formats but requires control of conjugation efficiency and residual free ligand. Post-insertion fusion may support payload compatibility and process flexibility, while requiring optimization of conjugation completeness, particle consistency, and product stability.
CATUG integrated support
CATUG supports targeted LNP-enabled in vivo cell therapy programs through plasmid template generation, RNA drug substance manufacturing, LNP/tLNP formulation development, ligand-conjugation feasibility, analytical method development, GMP drug product manufacturing, and CMC documentation. Our platform experience spans mRNA, circRNA, DNA/RNA payload-related workflows, multiple innovative lipid designs, and diverse delivery-system formats.
Why CATUG for targeted LNP-enabled cell therapy
Because targeted delivery performance is highly dependent on payload, target biology, ligand format, lipid chemistry, formulation design, and manufacturing process, CATUG supports these programs through project-specific feasibility assessment rather than one-size-fits-all platform claims. Integrated payload, delivery, analytics, and GMP-oriented manufacturing capabilities help clients identify developable formulation strategies and move toward IND-enabling studies and clinical translation.
CATUG supports non-viral in vivo CAR and targeted immune-cell engineering programs through integrated mRNA / circRNA payload strategy, RNA drug substance manufacturing, targeted LNP / tLNP formulation, ligand-conjugation feasibility, analytical development, GMP-oriented manufacturing, and CMC documentation.
in vivo CAR shifts the CMC focus from ex vivo cell processing to CAR-encoding payload design, targeted delivery, expression control, analytical characterization, and GMP-scalable drug product manufacturing.
Traditional CAR-T programs rely on cell collection, ex vivo genetic modification, expansion, release testing, logistics, and reinfusion, creating a complex vein-to-vein manufacturing model.
Non-viral in vivo CAR programs combine a CAR-encoding nucleic acid payload with a delivery system capable of selective immune-cell targeting, intracellular release, and functional CAR expression.
A successful in vivo CAR CMC strategy must connect payload, targeting, safety, analytics, and manufacturability.
Can the payload drive sufficient and durable CAR expression?
Can the delivery system reach the intended immune-cell population?
Can off-target exposure and process-related risks be controlled?
Can the process translate into a reproducible GMP workflow?
CATUG’s targeted LNP platform supports ligand-enabled delivery development from conjugation feasibility and analytical characterization to scale-up readiness for immune-cell targeting and in vivo CAR-related programs.
Different in vivo CAR and targeted delivery programs may require different engineering routes depending on payload type, ligand format, conjugation chemistry, formulation compatibility, and scale-up requirements.
Suitable for small molecules and payload co-formulation strategies where direct encapsulation contributes to targeted delivery performance.
Suitable for antibodies, antibody fragments, nanobodies and peptides for immune-cell or disease-relevant cell targeting.
Suitable for aptamers and ligand-enabled tLNP optimization where flexible post-formulation insertion is preferred.
Supports CAR-encoding RNA payloads and emerging complex payload strategies, with stage-appropriate RNA DS development, integrity control, and expression-profile evaluation.
Supports feasibility exploration for antibody, antibody-fragment, nanobody, peptide, aptamer, small-molecule, and ligand-enabled targeting strategies where applicable.
Development can address ligand density, conjugation efficiency, free ligand clearance, residual mAb or ligand control, positive percentage, and tLNP-specific analytical needs.
Supports formulation screening, lipid composition optimization, RNA loading, encapsulation efficiency, particle size tuning, PDI control, and process robustness.
Analytical support may include RNA integrity, particle attributes, ligand density, positive percentage, residual impurities, release testing, stability, binding activity, and potency-related method coordination.
Supports GMP-oriented process transfer, scale-up readiness, batch execution, fill-finish where applicable, release testing, CoA, batch records, and CMC source documentation.
in vivo CAR development requires coordinated evaluation of target biology, payload expression, tLNP targeting strategy, conjugation route, formulation robustness, analytical control, and GMP translation.
Built for non-viral in vivo CAR and targeted immune-cell engineering programs where payload expression, targeting strategy, conjugation chemistry, particle attributes, analytical characterization, and GMP manufacturability must be evaluated together.