Faster, Simpler T-Cell Targeting for In Vivo and Ex Vivo Applications
G-Link is a first-in-class adaptor protein that binds to lentiviral (LV) vectors, masks native receptor entry, and retargets delivery to resting T-cells.
Vyriad’s scalable, plug-and-play protein cap technology simplifies lentiviral-based T-cell targeting for both in vivo and ex vivo approaches. By detargeting the viral vector and redirecting it to CD3, G-Link enables more precise delivery with minimal modification.
Conventional CAR T manufacturing relies on “unblinded” viral envelopes and additional stimulatory components (e.g. CD3/28 beadsand targeting ligands), increasing complexity and risk of off-target effects. G-Link streamlines this process—enabling direct in vivo targeting and faster, simplified ex vivo workflows.
Key Benefits:
- Increased transduction efficiency
- Highly precise, cell-specific targeting without vector redesign
- Enhanced stability and resistance to complement
- Long-term durability of therapeutic response
- Faster time to therapeutic infusion
Engineered for Stable Binding and Retargeting
G-Link is built on an anti-LDLR domain that binds to the wild-type G protein on lentiviral vectors, enabling high-avidity attachment. The G-Link cap is designed to release in the endosome, allowing normal cell membrane fusion.
A trimerization linker connects this domain to an anti-CD3 scFv (UCHT1-derived), retargeting the vector specifically to T-cells. Together, these components mask native LDLR entry while retargeting delivery to CD3.
G-Link’s trimeric design increases CD3 binding (~100x) and improves overall stability across in vivo and ex vivo workflows.
Simplified In Vivo T-Cell Targeting
For in vivo workflows, G-Link is added to manufactured LV vectors, where it masks native receptor entry and redirects delivery to T-cells—without the need for complex vector redesign.
Faster T-Cell Booster Workflows
In ex vivo applications, G-Link is a plug-and-play adaptor protein that enables T-cell activation and enhanced transduction in a single step. Added alongside viral vectors directly to PBMCs, it integrates seamlessly into existing workflows—eliminating the need for vector redesign and accelerating manufacturing.
Key Platform Validation Results
The G-Link platform has been validated across key performance metrics including avidity, dose response (off-target binding), and anti-tumor activity.
CD3-dependent transduction enables selective T-cell delivery
GFP-encoding lentivirus pseudotyped with VSV-G was used directly (“Without G-Link”) or following retargeting with G-Link (With G-Link) to transduce Jurkat and Jurkat-TCR-KO cells (500 LVP/cell). GFP cells were imaged and quantitated 3 days post transduction.
Enhanced CAR expression in resting primary T-cells
Human PBMCs were transduced at 1000 LVP/cell with GFP-encoding (top) or BCMA-CAR-encoding (bottom) lentiviruses pseudotyped with VSV-G. Lentiviruses were used directly (left) or retargeted using G-link (right) for transduction.
Receptor masking increases with G-Link concentration
GFP-encoding lentivirus was incubated with buffer alone (WT-G LV) or the indicated amounts of G-Link CD3 and then used to transduce CD3+ T cells (Jurkat) or CD3- B cells (Nalm6). Fluorescence was imaged after 3 days.
Anti-tumor activity demonstrated in a multiple myeloma model
NSG DKO mice bearing BCMA+ OPM2-luciferase tumors were humanized with PBMCs. One week later (Day 0), mice were injected via tail vein with saline control, WT-G LV only (WT-G), G-Link CD3 only (G-Link), or BCMA-CAR lentivirus retargeted with G-Link CD3 (WT-G + G-Link). Tumor burden was monitored over time by bioluminescence imaging.
Curious about testing G-Link in your lab?
As part of our early evaluation program, Vyriad is currently offering complimentary G-Link materials to researchers interested in exploring the technology. Submit your information below and our team will review your request and follow up with next steps.
Moving beyond evaluation?
If you’ve already evaluated G-Link or are ready to incorporate it into your workflow at scale, you can also purchase G-Link directly through our distribution partner, Imanis Life Sciences.
Interested in more data?
Contact g-link@vyriad.flywheelstaging.com to request additional materials.