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Mertk gene therapy. It’s the first therapy for this rare retinal .
- Mertk gene therapy. Dec 14, 2021 · MERTK gene replacement therapy is considered as a promising treatment for MERTK-associated RP and demonstrated therapeutic efficacy (20 – 23). This review article touches upon the mechanisms of gene therapy, various enzymes of the visual cycle responsible for different genetic diseases, Luxturna—the first US Food and Drug Jan 1, 2022 · Here, we examine the rationale of Mertk-targeted immunotherapies, the current and potential therapeutic strategies, the clinical status of Mertk-specific therapies, and potential challenges and obstacles for Mertk-focused therapies. Recent studies have indicated that the use of Gas6 enhances retinal phagocytosis via the MERTK receptor either alone or in combination with other specific ligands for receptor tyrosine kinases, which Jun 30, 2025 · Advancing Therapy for an Unmet Need OPGx-MERTK is currently in preclinical development, targeting a rod-cone dystrophy characterized by early macular atrophy, with retinitis pigmentosa being the most common clinical presentation. Recent studies have indicated that the use of Gas6 enhances retinal phagocytosis via the MERTK receptor either alone or in combination with other specific ligands for receptor tyrosine kinases, which Jul 12, 2024 · The more physiologic role of MERTK began to be revealed at UNC when working with Bev Koller, who had trained with the pioneer of gene targeting Oliver Smithes, and our group made a Mertk knockout (Mertk-/-) mouse. MERTK RP patients with a mutation of the receptor tyrosine kinase gene, MERTK, have a defective phagocytosis pathway in the RPE that leads to retinal degeneration [38]. Mar 8, 2013 · Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral vectors in the Royal College of Surgeon (RCS) rat, a well characterized model of recessive retinitis pigmentosa that contains a mutation in the Mertk gene. Oct 4, 2024 · Mechanistic studies further revealed that ALK And LTK Ligand 1 (ALKAL1), a target gene of aryl hydrocarbon receptor (AhR), facilitated MerTK phosphorylation, resulting in heightened phagocytic activity of MerTK + macrophages and their subsequent polarization toward an immunosuppressive phenotype. Jun 1, 2013 · PDF | On Jun 1, 2013, Thomas J. May 12, 2025 · On May 13, at the ASGCT Annual Meeting, they will discuss their investigational gene therapy OPGx-MERTK, which aims to treat MERTK-related retinitis pigmentosa, showcasing promising Conlon TJ, Deng WT, Erger K, et al. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into … May 12, 2025 · OPGx-MERTK (AAV2-VMD2-hMERTK) is an investigational gene therapy developed by Opus Genetics to treat patients with MERTK-related RP. Jan 1, 2015 · MERTK-associated retinal degenerations are thought to have defects in phagocytosis of shed outer segment membranes by the retinal pigment epithelium (RPE), as do the rodent models of these diseases. Aug 4, 2019 · Purpose We investigated the effects of various retinal laser therapies on preservation of the photoreceptors in an animal model of Mer tyrosine kinase receptor (MERTK)–related retinitis pigmentosa (RP). Apr 18, 2012 · The absence of Mertk in RCS rats results in defective RPE phagocytosis, accumulation of outer segment (OS) debris in the subretinal space, and subsequent death of photoreceptors. Summary of gene and mutations by cancer type from ICGC MERTK Cancer Genome Anatomy Project, NCI Gene Summary MERTK COSMIC, Sanger Institute Somatic mutation information and related details MERTK GEO Profiles, NCBI Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus The more physiologic role of MERTK began to be revealed at UNC when working with Bev Koller, who had trained with the pioneer of gene targeting Oliver Smithes, and our group made a Mertk knockout (Mertk-/-) mouse. Physiologic r… Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Aug 1, 2003 · The results described here therefore provide strong support for developing AAV-based gene therapy approaches for RP patients with mutations in MERTK. i) Phagocytosis-related genes were separated into those with significant changes in red, and those with no change following Oct 4, 2024 · Specifically targeted delivery of AhR antagonist to tumor-associated macrophages with mannosylated micelles could suppress MerTK expression and improved the therapeutic efficacy of anti-programmed cell death ligand 1 therapy. Previous research utilizing Mertk gene replacement therapy in RCS rats provided Here, we examine the rationale of Mertk-targeted immunotherapies, the current and potential therapeutic strategies, the clinical status of Mertk-specific therapies, and potential challenges and obstacles for Mertk-focused therapies. Journal Pre-proof A single nucleotide polymorphism in the MerTK gene is associated with increased radiological disease activity in patients with Multiple Sclerosis on natalizumab therapy Abstract Over 2 million people worldwide are suffering from gene-related retinal diseases, inherited or acquired, and over 270 genes have been identified which are found to be responsible for these conditions. 1. Moreover, one variant represents a single nucleotide transition, which is theoretically targetable with CRISPR-Cas9 base-editing. Specific ligands for receptor tyrosine kinases, such as growth arrest-specific 6 (Gas6), m … A single nucleotide polymorphism in the MerTK gene is associated with increased radiological disease activity in patients with multiple sclerosis on natalizumab therapy Mar 16, 2024 · Taken together, these data showed that Axl/MerTK gene expression, as well as Axl-/MerTK STRING modules and related pathways, are linked to synovial histopathology. However, aberrant expression in a … Aug 11, 2015 · Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. This inherited retinal disease, linked to mutations in the MERTK gene, affects an estimated 600 individuals in the United States. We also confirmed the re-establishment of the expression of full-length MERTK protein and the complete reversion of lost phagocytic function of RPE patches derived from gene-corrected RP-hiPSCs. IRD due to MERTK mutations represents an exciting opportunity for development of gene therapy. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. In the present study, we conducted a series of preclinical efficacy and safety evaluations of an AAV2 vector expressing human MERTK cDNA driven by a RPE-specific VMD2 promoter, including a formal GLP toxicology and biodistribution study. Find diseases associated with this biological target and compounds tested against it in bioassay experiments. OPGx-MERTK (AAV2-VMD2-hMERTK) is an investigational gene therapy developed by Opus Genetics to treat patients with MERTK-related RP. OPGx-BEST1 Nov 30, 2020 · D’Cruz PM, Yasumura D, Weir J, et al. MERTK plays a key role in renewal of ph … Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral vectors in the Royal College of Surgeon (RCS) rat, a well characterized model of recessive retinitis pigmentosa that contains a mutation in the Mertk OPGx-MERTK Mutations in the MERTK gene cause a rod-cone dystrophy with early macular atrophy, with retinitis pigmentosa being the most common phenotype. The defect results from a mutation in the Mertk gene, which is normally expressed in the RPE. MerTK rs7422195 SNP GA/AA is associated with a higher rate of radiological disease activity in MS treated with natalizumab. Results from a pre-clinical study which evaluated OPGx-MERTK in Jun 23, 2025 · NEW YORK – Opus Genetics on Monday said it plans to advance its preclinical gene therapy program for retinitis pigmentosa caused by pathogenic variants in the MERTK gene toward clinical trials, armed with up to $2 million in non-dilutive funding from the Retinal Degeneration (RD) Fund. 1. 05). Physiologic r… Abstract Proof of concept for MERTK gene replacement therapy has been demonstrated using different viral vectors in the Royal College of Surgeon (RCS) rat, a well characterized model of recessive retinitis pigmentosa that contains a mutation in the Mertk gene. Our analysis identified MERTK as a gene that is associated with organ fibrosis in multiple human and mouse tissues that are affected by persistent injury. Schematic of the MERTK gene (Accession Number NG_011607. Preclinical studies have shown proof of concept in rats and mice and an early clinical trial with an AAV vector was carried out several years ago with mixed results. We have subretinally injected an RPE-specific AAV2 vector, The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. B. These RTKs also function in normal innate May 12, 2025 · In this rat model of retinal degeneration, subretinal administration of OPGx-MERTK (1E10 vg/eye) demonstrated effective preservation of both photoreceptors and retinal function. Oct 1, 2025 · To isolate any potential effects of MerTK rs7422195 and HLA-DRB1*1501 genotype on MerTK expression on activated T cells from DR15 induced autoproliferation, assessing association between MerTK rs7422195 and HLA-DRB1*1501 genotype and disease activity under conditions of anti CD20 therapy, such as ocrelizumab or ofatumumab, would be of benefit. a. A. OPGx-MERTK: A gene therapy for MERTK-related Retinitis Pigmentosa (affecting 3% of RP cases), showing effective preservation of photoreceptors and retinal function in rat studies. It’s the first therapy for this rare retinal International Cancer Genome Consortium. The resulting accumulation of debris in the subretinal space leads to a progressive loss of photoreceptors. Mertk is a receptor In the Royal College of Surgeons (RCS) rat, the retinal pigment epithelium (RPE) cannot phagocytose the outer segment discs that are continually shed from photoreceptors. The most recent attempt to transfer MERTK via gene therapy took advantage of an AAV vector containing Y733F tyrosine-to-phenylalanine substitutions. This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023. Linkage disequilibrium (LD) structure for all Hapmap phase II CEU SNPs (release 24, build 36, forward strand) in the MERTK gene, visualized using Haploview v4. Mar 3, 2025 · In murine HCC MERTK is found in activated DC and macrophages that overexpress PD-L1. Mar 9, 2025 · Neurotech Pharmaceuticals’ surgically implanted cell and gene therapy, Encelto, is now FDA approved to treat macular telangectasia type 2 (MacTel). Apr 3, 2024 · Despite this strong genetic evidence, MERTK has not been explored as a potential therapeutic target for liver and for fibrotic diseases in other organs. Future studies in a Mertk knockout mouse model will test the efficacy of rAAV2-mediated MERTK gene therapy. Introduction 1. Jan 20, 2005 · In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA MERTK gene replacement therapy is considered as a promising treatment for MERTK-associated RP and demonstrated therapeutic efficacy (20 – 23). In order to overcome the short life effect of the injected Gas6 protein, we constructed a Sep 25, 2024 · High MERTK or low DC gene expression were associated with poor prognosis in pediatric ALL patients, indicating the clinical relevance of these findings. Jun 23, 2025 · About OPGx-MERTK Mutations in the MERTK gene cause a rod-cone dystrophy with early macular atrophy, with retinitis pigmentosa being the most common phenotype. 1, Chromosome 2: 12,656,056-112,787,138 forward strand). Jun 1, 2018 · Retinal degenerative diseases are a major cause of blindness. Retinal gene therapy is a trail-blazer in the human gene therapy field, leading to the first FDA approved gene therapy product for a human genetic disease. It’s the first therapy for this rare retinal Mar 9, 2025 · Neurotech Pharmaceuticals’ surgically implanted cell and gene therapy, Encelto, is now FDA approved to treat macular telangectasia type 2 (MacTel). Jun 23, 2025 · Funding will support preclinical development of OPGx-MERTK, a potential treatment for MERTK-related retinitis pigmentosa The clinical-stage biopharma company focused on developing gene therapies for inherited retinal diseases (IRDs) Opus Genetics (Nasdaq: IRD), announced it has secured up to $2 million in non-dilutive funding from the Retinal Degeneration Fund (RD Fund), the venture Nov 24, 2014 · The TYRO3, AXL and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are overexpressed in tumour cells, promoting cell survival and chemoresistance. MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. 2. Jan 1, 2022 · Mertk, first discovered in 1992 by Hanafusa and colleagues, was initially isolated as a truncated tyrosine kinase (Env-Ryk, v-Ryk, v-Eyk) from the transforming gene of chicken retrovirus RPL30 (Jia et al. Nevertheless, a number of issues will need to be addressed before a clinical trial might be considered. Sixteen years . The company will present data on:1. MERTK is a promising candidate for viral-mediated gene replacement therapy. Conclusions We report three missense variants in MERTK and present the associated phenotypic data, which are supportive of non-syndromic RP. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Apr 28, 2025 · Efferocytosis of apoptotic tumor cells by tumor-associated macrophages mediated through the phosphatidylserine (PtdSer)/MER proto-oncogene tyrosine kinase (MerTK) axis can exacerbate tumor immunosuppression, and conversely, prevention of efferocytosis via blocking PtdSer–MerTK association using prevalent antibodies represents a promising strategy for reversing tumor immunosuppression and Feb 5, 2024 · In these circumstances, MerTK gene therapy may enable immune cells to improve cell efferocytosis and enhance therapeutically exploit cancer immunotherapy to enhance immune cell clearance of dying cancer cells. Mar 5, 2025 · OPGx-MERTK is a gene therapy being developed by Opus Genetics to treat patients impacted by MERTK-related retinitis pigmentosa (RP). May 12, 2025 · In this rat model of retinal degeneration, subretinal administration of OPGx-MERTK (1E10 vg/eye) demonstrated effective preservation of both photoreceptors and retinal function. 27 Since RPE phagocytosis is the primary defect in MERTK- related IRD, 5 the target of gene augmentation therapy is RPE cells which may be more amenable to gene augmentation than photoreceptors that are undergoing retinal degeneration. Discovery and expression of Mertk Mar 5, 2025 · OPGx-MERTK is a gene therapy being developed by Opus Genetics to treat patients impacted by MERTK-related retinitis pigmentosa (RP). In the Royal College of Surgeons (RCS) rat, the retinal pigment epithelium (RPE) cannot phagocytose the outer segment discs that are continually shed from photoreceptors. Conlon and others published Preclinical Safety Studies for AAV2-MerTK Gene Therapy Vector for Retinitis Pigmentosa | Find, read and cite all the research you need The intermediate steps between Mertk activation and movement of myosin II to sites of OS ingestion, including possible actin cytoskeletal changes, are unknown. We have subretinally injected an RPE-specific AAV2 vector, May 12, 2025 · Opus Genetics (Nasdaq: IRD) announced upcoming presentations of its inherited retinal disease (IRD) gene therapy programs at three scientific conferences in May 2025. Another opportunity lies in gene replacement therapy for MERTK -associated retinal disease. The mechanism of MERTK -related retinal degeneration has been well-characterized in pre-clinical models, permitting proof-of-concept studies. CD11b + Gr1 lo IA + macrophages sorted from untreated and irradiated tumors were subjected to gene expression analysis (GEO accession number GSE34206). Sep 2, 2016 · Figure 1: Upregulation of the macrophage-specific phagocytic receptor Mertk following radiation therapy of tumors. Apr 1, 2024 · In these circumstances, MerTK gene therapy may enable immune cells to improve cell efferocytosis and enhance therapeutically exploit cancer immunotherapy to enhance immune cell clearance of dying cancer cells. These modalities included photocoagulation with various pattern densities, selective RPE therapy (SRT), and nondamaging retinal therapy (NRT). Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and platelet aggregation. Preclinical potency and safely studies of an AAV2-mediated gene therapy vector for the treatment of MERTK associated retinitis pigmentosa. 2 Discover advanced gene therapy strategies for blindness at ASGCT 2025, featuring innovative cell based assays and transformative treatments for inherited vision loss. Mertk is a receptor Dec 14, 2021 · Previous researches utilizing MER proto-oncogene tyrosine kinase (MERTK) gene therapy in Royal College of Surgeons (RCS) rats evidenced its effectiveness in treating MERTK-associated retinitis pigmentosa (RP). However, MERTK is over-expressed or ectopically expressed in a wide variety of cancers, including leukemia, non-small cell lung Oct 1, 2025 · A single nucleotide polymorphism in the MerTK gene is associated with increased radiological disease activity in patients with multiple sclerosis on natalizumab therapy Feb 20, 2024 · MerTK blockade might be efficacious to counter this resistance and sensitize HCC to anti-PD-L1 therapy. For example, MerTK inhibition emerges as a new strategy for cancer therapy due to it counteracts effect on anti-tumor immunity, while MerTK restoration represents a promising treatment for atherosclerosis and myocardial infarction as MerTK is cleaved in these disease conditions. The purpose Oct 1, 2021 · MERTK- related IRDs represent an attractive candidate for gene therapy for several reasons. May 5, 2025 · Tumor-associated MerTK promotes a pro-inflammatory microenvironment and enhances immune checkpoint inhibitor response in triple-negative breast cancer Aug 23, 2024 · For sequence alignment, shRNA target sequences were mapped to reference gene sequences of Tyro3 (gene ID: 7301), Axl (gene ID: 558) and Mertk (gene ID: 10461) using Geneious prime with sensitivity Mar 5, 2025 · OPGx-MERTK is a gene therapy being developed by Opus Genetics to treat patients impacted by MERTK-related retinitis pigmentosa (RP). The application of Clustered Regularly Interspaced Jun 23, 2025 · This funding underscores its continued commitment to supporting high-impact programs for rare diseases and will help accelerate the preclinical studies required to advance regulatory filings for the OPGx-MERTK program, further strengthening Opus’ gene therapy pipeline for IRDs. Sep 1, 2020 · The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. May 12, 2025 · OPGx-MERTK (AAV2-VMD2-hMERTK) is an investigational gene therapy developed by Opus Genetics to treat patients with MERTK-related RP. , 1992). However, MERTK is over-expressed or ectopically expressed in a wide variety of cancers, including leukemia, non-small cell lung cancer, Jul 12, 2025 · This funding underscores its continued commitment to supporting high-impact programs for rare diseases and will help accelerate the preclinical studies required to advance regulatory filings for the OPGx-MERTK program, further strengthening Opus’ gene therapy pipeline for IRDs. Knockout and knockdown of MerTK reduced cell proliferation and migration both in vitro and in vivo. 2000;9 (4):645-651 Feng W, Yasumura D, Matthes MT, LaVail MM, Vollrath D. Specific ligands for receptor tyrosine kinases, such as growth arrest-specific 6 (Gas6), may enhance retinal phagocytosis via the MERTK receptor, and consequently, enhance the therapeutic effects of gene therapy. Jan 23, 2025 · Explore clinical updates and promising results of AAV9-MERTK gene therapy for retinitis pigmentosa, a cutting-edge treatment aimed at preserving retinal structure and improving vision. The funding will support preclinical development for treating retinitis pigmentosa caused by MERTK gene variants, a condition currently without approved treatments [1]. Black rectangles indicate the 19 exons of MERTK and grey lines show physical location of the 12 replicated SNPs. Additionally, MerTK could serve as biomarkers for screening patients with HCC using sitravatinib plus anti-PD-L1 combination therapy. Lancelot, the Briard dog that was treated, suffered from a human childhood blindness called Leber's congenital amaurosis type 2. This had been shown to provide rapid and efficient reporter-gene expression when injected subretinally into adult mouse eyes. The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. MERTK-associated retinitis pigmentosa (RP). MERTK is a receptor tyrosine kinase of the TAM (Tyro3, Axl, MERTK) family, with a defined spectrum of normal expression. Apr 1, 2013 · The Current Status of the Use of Gene Therapy in Ophthalmology Four retinal diseases could see genetic therapies sooner rather than later. Results from a pre-clinical study which evaluated OPGx-MERTK in a rat model of RP will be presented at ARVO. Hum Mol Genet. This shows efficacy of MERTK gene augmentation by gene therapy in preserving retinal structure and function in a murine model of MERTK mutation and RPE defect. Conclusions : Herein, we show that OPGx-MERTK can prevent retinal degeneration in RCS rats, when treated by single bilateral subretinal injection at p14. Six patients were entered in a phase I open-label, dose-escalation Mar 28, 2024 · Results In patients, high MerTK expression was associated with decreased overall survival (OS) and lymph node metastasis especially in patients without neoadjuvant therapy (p < 0. IRV ARONS With the first approval of a gene therapy for treating a genetic disorder in the Western world, the future of gene therapy for treating ocular disorders looks bright. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. 33 The rAAV-MERTK vector led to longer and more robust functional and Jan 29, 2016 · MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. In studying the gene expression patterns of tumor infiltrating macrophages, we identified upregulation of Mertk in tumor macrophages following radiation therapy. Oct 10, 2013 · MERTK is a receptor tyrosine kinase of the TAM (Tyro3, Axl, MERTK) family, with a defined spectrum of normal expression. Aug 29, 2022 · Conclusions We report three missense variants in MERTK and present the associated phenotypic data, which are supportive of non-syndromic RP. A single nucleotide polymorphism in the MerTK gene is associated with increased radiological disease activity in patients with multiple sclerosis on natalizumab therapy In 2001, the first large animal was successfully treated with a gene therapy that restored its vision. rAAV2-VMD2-hMERTK is an AAV2 vector that was altered to carry the human MERTK gene for the treatment of patients with RP due to mutations in the MERTK gene. Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. MERTK-associated retinal degenerations are thought to have defects in phagocytosis of shed outer segment membranes by the retinal pigment epithelium (RPE), as do the rodent models of these diseases. The therapy is designed as a modern Jun 23, 2025 · Opus Genetics (Nasdaq: IRD) has secured up to $2 million in non-dilutive funding from the Retinal Degeneration Fund (RD Fund) to advance its OPGx-MERTK gene therapy program. Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and Jun 23, 2025 · This funding underscores its continued commitment to supporting high-impact programs for rare diseases and will help accelerate the preclinical studies required to advance regulatory filings for the OPGx-MERTK program, further strengthening Opus’ gene therapy pipeline for IRDs. Combination of ICI with MERTK inhibition results in improved therapeutic efficacy, indicating that MERTK could be a promising target for combinatorial immunotherapies in HCC patients with tumors enriched in myeloid cells. Here, we examine the rationale of Mertk-targeted immunotherapies, the current and potential therapeutic strategies, the clinical status of Mertk-specific therapies, and potential challenges and obstacles for Mertk-focused therapies. Gene correction of one or both alleles restored MERTK expression lost in the patient's cells. Jul 5, 2025 · Gene target information for MERTK - MER proto-oncogene, tyrosine kinase (human). Apr 28, 2025 · Our findings provide a reliable gene-editing-mediated strategy for long-term modulating MerTK homeostasis and overcoming MerTK-dependent cancer immune evasion, generating adaptive antitumor immune responses for sustained cancer immunotherapy. The RD Fund We also delve into new therapeutic approaches such as gene therapy, stem cell transplantation and genome surgery, which are designed to either replace or repair the damaged photoreceptors to restore vision and ultimately enhance the life of the RP patient. wzt kilu 4kts9 rblm vj8 obc k7 pkn z9in8o liitfk