IN VIVO CAR-T · TARGETED LVV · BAY AREA, USA
From cell-specific promoter and construct engineering through cGMP lentiviral vector, fill/finish and release — one integrated partner for in vivo CAR-T programs, with no vendor handoffs between the sequence and the vial.
LENTIVIRAL MANUFACTURING SERVICES
Integrated synthetic biology research, in vivo gene therapy expertise and cGMP vector manufacturing meet under one roof.
We optimize the genetic elements — cell-specific promoters, cassette orientation, regulatory elements — and manufacture the lentiviral vector that delivers them directly to patients.
The engine of the therapy. Lentivirus and gamma-retrovirus production from adherent 2–20 L to suspension GMP 50–200 L, in closed and functionally closed systems.
T cell-specific promoters available for integration into your construct, plus ML-driven sequence optimization, regulatory element design and custom producer cell line engineering.
FROM DESIGN TO DRUG PRODUCT
An in vivo lentiviral program is rarely linear. We treat the journey — from genetic design through IND-enabling and clinical to commercial supply — as one continuous platform. Below are the capabilities that platform stitches together, not stops along a conveyor belt.
Construct system for in vivo CAR-T LVV drug product
In vivo lentiviral vector workflow
SYNTHETIC BIOLOGY
Promoter conventions in current lentiviral vectors were inherited from ex vivo practice, where transgene expression during manufacture carried little consequence. Directly administered, that inheritance becomes a risk — and a solvable one, at the level of the construct.
THE PROBLEM · BREAKTHROUGH EXPRESSION
What the producer cell makes ends up on the particle.
Lentiviral particles bud from the producer cell membrane and carry away whatever is sitting in it — including your CAR, if the producer cell transcribed it during manufacture.
The producer cell spends biosynthetic capacity on a protein it has no use for. Most batch cost is fixed, so lost titer raises cost per dose almost proportionately.
Surface-displayed CAR directs particles toward antigen-positive cells, competing with the binder and fusogen you engineered. A second specificity nobody specified.
Displayed receptor binds shed antigen and is consumed by cells that were never the intended recipients. Dose rises, and with it batches per patient.
An envelope whose composition varies with transgene expression is harder to specify, release and defend at every subsequent process change.
Batches per patient is the ratio of doses recovered to particles required, so reductions in titer and escalations in dose multiply rather than add — on a batch cost that is largely fixed.
THE APPROACH · PROMOTER AND CASSETTE
A problem no process parameter reaches, closed at the construct.
Breakthrough expression has two routes into the producer cell: the internal promoter, and the genomic transcript itself when the cassette sits in sense. A T cell-specific promoter closes the first. Inverting the cassette closes the second. Neither is sufficient alone — and taken together they raised functional titer rather than costing it.
We engineer the promoter, design the cassette around it, and manufacture the drug product it goes into. The whitepaper below sets out the mechanism, the four-configuration comparison and the titer data behind it.
Where today’s promoter conventions came from, why the producer cell transcribes your transgene, what it costs in CMC terms, and the construct-level resolution — with the flow cytometry, imaging and functional titer data behind it.
Whitepaper · 8 pages · GeneFab, 2026
THE RESULT · T CELL-SPECIFIC PROMOTERS
Silent in the producer cell. Strong in the target cell.
Our T cell-specific promoters are available for integration into your own construct, alongside your payload, binder and fusogen. Each is specified against three constraints at once: functionally inactive in the production line and in off-target tissue, strong enough in the target cell to deliver therapeutic expression, and compact enough — under 750 bp — to leave transgene capacity intact.
QUALITY, RELEASE AND TRANSFER
Release testing, microbiology and raw material testing are in-house on the same site as the batch, so investigations and deviations don’t add vendor scheduling to a clinical timeline. Methods are qualified phase-appropriately and run on a standing cadence.
COMMON QUESTIONS
Adherent 2 to 20 L for early and IND-enabling material, and suspension to 200 L GMP, in seven Grade B suites at Alameda. Upstream and downstream development for yield and purity is part of process development rather than a separate engagement, and scale-up strategy covers G-Rex, Wave, Vertical Wheel and stir tank.
Yes. Construct and promoter design, plasmid and producer system, process and analytical development, cGMP vector manufacture, formulation and fill/finish into bags or vials, full release panel including vector copy number, stability, and CMC authoring for IND, IMPD or BLA — on our own sites, under one quality system.
That is a large part of what we do. Transfer starts with a structured gap assessment across process, analytical and quality, plus a risk assessment read out of your batch records before kickoff, followed by engineering runs with delta analysis. Development-to-GMP transfer typically runs about seven months; commercial-to-commercial programs can run up to twenty-four.
Yes. Microbiology — endotoxin, sterility, mycoplasma and environmental monitoring — plus raw material testing and the full release panel, with method validation to USP and EP standards. Keeping analytics on the same site as the batch is what keeps deviations from adding weeks.
It did not in our hands. A T cell-specific promoter in a cassette inverted relative to the vector genome gave the highest functional titer of the four configurations tested, while potency in primary T cells held at 34% of the EF-1α control. The titer penalty people expect comes from convergent transcription, which only arises when the internal promoter is still active in the producer cell.
Yes — that is how they are intended to be used. They are payload-agnostic and under 750 bp, and it was characterized in the HEK293 system the material will be made in, so there is no re-qualification in a different host cell. What transfers directly and what needs bridging for your payload and indication is program-specific, and is what a project review establishes.
Improved LVV Manufacturing for In Vivo CAR-T Through Synthetic Biology-Guided Promoter Design. Please tell us who you are — all fields required.
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Send the payload, the target cell, and what already exists — construct, process, analytics, current vendors. We’ll come back with a view on promoter selection and cassette orientation, what transfers as-is, what needs bridging, and the route to GMP drug product. contact@genefab.com
