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 -1), mice were injected via tail vein with saline control, G-Link CD3 only (Saline + G-Link CD3), or BCMA-CAR encoding lentivirus retargeted with G-Link CD3 (LV-CAR + G-Link CD3). Tumor burden was monitored over time by bioluminescence imaging.
Ready to start testing?
Interested in more data? Contact g-link@vyriad.com to request additional materials.
Interested in more data?
Contact g-link@vyriad.com to request additional materials.