Vyriad has introduced G-Link, a modular platform designed to enhance T-cell targeted lentiviral vector delivery for both in vivo and ex vivo therapeutic applications.
Vyriad, Inc. has introduced a new modular adaptor protein technology called G-Link™, a platform designed to improve targeted delivery for both in vivo and ex vivo CAR T-cell therapies. The company unveiled the technology during presentations at the 2026 American Society of Gene & Cell Therapy Annual Meeting, where researchers highlighted preclinical data demonstrating the platform’s ability to enhance precision, scalability, and efficiency in T-cell-targeted gene delivery workflows.
The announcement marks a significant step for Vyriad as the biotechnology industry continues searching for practical and scalable solutions to one of the most persistent challenges in gene and cell therapy development: efficient and selective delivery of genetic material to target cells. In particular, in vivo CAR T-cell therapy — where immune cells are engineered directly inside the patient’s body rather than through external manufacturing processes — has emerged as a promising but technically complex frontier in cancer treatment.
According to Vyriad, G-Link was developed to address many of the limitations associated with current viral vector targeting strategies. The company described the technology as a first-in-class “plug-and-play” adaptor system capable of redirecting standard lentiviral vectors toward CD3-positive T cells without requiring extensive vector redesign or complicated manufacturing modifications.
The platform was developed in collaboration with Menachem Rubinstein and builds upon the established performance characteristics of vesicular stomatitis virus G glycoprotein, commonly referred to as VSV-G, which is widely used in lentiviral vector systems. Traditionally, VSV-G-pseudotyped lentiviral vectors naturally bind to low-density lipoprotein receptors, or LDLRs, resulting in broad cellular tropism rather than selective targeting.
Vyriad’s G-Link technology is designed to mask this native LDLR tropism while redirecting vector delivery specifically toward CD3-positive T cells. The company explained that the adaptor uses a trimeric architecture capable of simultaneously engaging the three protomers of the VSV-G protein. This creates high-avidity binding to the viral envelope while enabling selective interaction with T cells and potentially other cell types.
Once the viral particle enters the target cell, the G-Link adaptor is released within the endosome, allowing normal membrane fusion and preserving overall vector function. According to the company, this mechanism enables selective targeting without disrupting the underlying performance and manufacturing advantages of conventional VSV-G lentiviral vectors.
Luke Russell said the gene and cell therapy industry increasingly recognizes delivery as one of the largest barriers to advancing in vivo CAR T-cell therapies. He noted that many existing approaches involve complicated vector redesign strategies or manufacturing processes that may limit scalability and operational simplicity.
Russell stated that G-Link was specifically developed to remove those barriers by providing a flexible and practical delivery solution capable of accelerating innovation in both in vivo and ex vivo CAR T-cell workflows. He emphasized the importance of maintaining simplicity at a time when the industry is seeking scalable manufacturing and clinical development pathways.
During the ASGCT presentations, Vyriad shared preclinical findings demonstrating the use of G-Link-capped lentiviral vectors carrying the same anti-BCMA CAR construct used in the company’s lead in vivo CAR T-cell candidate, VV169. The vectors were pseudotyped with wild-type VSV-G and evaluated in a disseminated multiple myeloma xenograft model using OPM-2 human tumor cells.
The lentiviral system incorporated a modified T-cell-selective promoter within a reversed expression cassette designed to drive CAR expression specifically in T cells while preventing incorporation of the CAR construct into the viral envelope during packaging. According to the company, this design may help reduce the risk of off-target transduction in malignant cells.
Researchers reported that the G-Link-enabled vectors generated functional CAR T cells directly in vivo and demonstrated substantial anti-tumor activity in the preclinical model. Among the most notable findings was complete tumor clearance occurring between days 14 and 28 following treatment, including in animals receiving the lowest tested dose levels.
Vyriad also reported that CAR T cells became detectable by day 14 after treatment and declined after tumor elimination, suggesting an immune response correlated with disease clearance. Importantly, animals remained tumor-free even after tumor rechallenge, indicating the potential development of sustained anti-tumor immunity.
The company further stated that treatment appeared to be well tolerated in preclinical studies. Investigators observed minimal cytokine elevation, stable body weight, and no significant toxicities during the experiments, findings that may support future clinical translation efforts.
Additional studies presented at ASGCT evaluated the stability and robustness of the G-Link system under manufacturing and clinical translation-related conditions. According to Vyriad, the platform maintained targeting performance and tropism despite freeze-thaw stress, downstream purification procedures, room-temperature exposure, highly diluted formulations, and detergent-heavy environments.
Beyond in vivo CAR T-cell applications, Vyriad also highlighted the versatility of G-Link in ex vivo gene delivery workflows. In these settings, the adaptor technology functions as a transduction enhancer that improves T-cell activation and gene delivery efficiency when used alongside standard wild-type lentiviral vectors.
The company explained that G-Link enables efficient transduction without requiring additional T-cell sorting or activation procedures, potentially simplifying manufacturing workflows for ex vivo CAR T-cell therapies.
Researchers compared G-Link-capped lentiviral vectors against engineered CD3-targeted vectors in studies involving a CAR construct directed against prostate-specific membrane antigen, or PSMA, a protein highly expressed in prostate cancer cells. According to the data presented, both delivery platforms generated high-titer CD3-targeted vectors capable of selectively transducing CD3-positive cell populations within peripheral blood mononuclear cells and Jurkat T-cell lines.
Importantly, investigators reported no detectable transduction in CD3-negative cell lines, suggesting high targeting specificity. The transduced T cells successfully expressed the anti-PSMA CAR construct and demonstrated functional activation through upregulation of CD25 expression, a marker associated with T-cell activation.
Vyriad also presented data suggesting that the G-Link platform may extend beyond lentiviral vector systems. Additional studies demonstrated the ability of the adaptor technology to retarget engineered virus-like particles carrying Cas9 gene-editing machinery.
In a beta-2 microglobulin knockout study, G-Link successfully blocked LDLR-mediated cellular entry while promoting efficient CD3-specific gene editing activity. These findings suggest the platform may have broader applications across multiple gene delivery and genome-editing technologies.
Kah-Whye Peng said the greatest opportunity associated with G-Link lies in the development flexibility it introduces. According to Peng, the platform enables both Vyriad and its collaborators to pursue new therapeutic targets and applications without being constrained by extensive vector redesign requirements.
He noted that the technology could significantly accelerate the speed and breadth with which development programs move forward across the gene and cell therapy landscape.
For research applications, Vyriad indicated that G-Link is currently available commercially through Imanis Life Sciences, potentially enabling broader adoption among academic and industry researchers evaluating targeted delivery technologies.
Meanwhile, the company’s lead in vivo CAR T-cell program, VV169, is expected to enter clinical development later this year. Vyriad stated that the G-Link platform itself will continue advancing toward future clinical translation as the company seeks to expand its broader pipeline of targeted genetic therapies.
The introduction of G-Link arrives amid increasing industry interest in technologies capable of simplifying CAR T-cell manufacturing and enabling direct in vivo engineering of immune cells. As companies continue pursuing more scalable and accessible cell therapy approaches, adaptable delivery platforms such as G-Link may play an increasingly important role in overcoming current technical and operational limitations within the field.
About Vyriad
Vyriad is a clinical-stage biotechnology company developing targeted genetic medicines for cancer and other serious diseases. The company uses engineered viruses, viral vectors, and viral envelope glycoproteins to deliver therapeutic genes directly to selected cells. Vyriad’s programs include oncolytic virotherapy, in vivo gene therapy, and gene editing applications, with ongoing Phase 1–2 trials in multiple cancer indications. Vyriad is a privately held company based in Rochester, Minnesota.
