uniQure's Technology:

Pioneers in the Field of Gene Therapy

uniQure has built an industry-leading gene therapy platform
Focused on liver-directed and central nervous system disorders.

Gene therapy offers the prospect of long-term and potentially curative benefits to patients with genetic or acquired diseases by directing the expression of a therapeutic protein or restoring the expression of a missing protein through a single administration. > Gene therapy information (PDF)

Genes are the specific areas of DNA that provide the blueprint used by the body’s cellular machinery to make proteins. A defect or mutation in a specific gene can result in the inability or reduced ability to express a protein, or the reduced functionality of a protein. For example, when the gene associated with the production of a protein required for blood clotting is missing or mutated in hemophilia B patients, these patients’ blood cannot clot enough to stop bleeding, even after a minor trauma or surgery. Introducing a copy of the proper gene into the cell could restore the presence and natural function of the blood-clotting factor, which would prevent bleeding.

 See below for an animated demonstration of how gene transfer technology functions within the body:

 

uniQure develops its gene therapies using an innovative and modular technology platform, including our proprietary, cost-effective manufacturing process. An overview of our key patent portfolio can be found here.   

Our gene therapy technology consists of three key elements:

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A therapeutic gene in a “gene cassette” that corrects the defective or missing protein, restoring function or silencing a disease-causing effect in target cells. 

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Therapeutic Gene Cassettes

We design our own gene therapies to deliver a transgene into the body’s cells to encode for the expression of a therapeutic protein or RNA construct. The transgene is carried in a gene cassette together with DNA promoters that direct expression in specific tissues.

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An AAV-based vector delivery system for delivering the gene cassette

 

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Best-in-Class AAV-based Vector Delivery System
We deliver the gene cassette to the target tissue using an engineered, non-replicating viral vector delivery system based on AAV (adeno-associated virus). Researchers have used AAV-based vectors in pre-clinical research and over 80 clinical trials in which AAV-based vectors have demonstrated a good safety profile. AAVs have also demonstrated lasting therapeutic gene expression following a single treatment in preclinical and clinical studies. 

We use the AAV5 variant, or serotype, of vector in our product candidates in hemophilia B and Huntington's disease, and have exclusive, worldwide rights to AAV5 for use in therapeutic products delivered to the brain or liver. Our research suggests that a greater portion of patients can be effectively treated with AAV5 gene therapy, compared to other AAV-based gene therapies. 

AAV5-based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials, including five uniQure trials conducted in nearly 80 patients in hemophilia B and other indications. No patient treated in clinical trials with the uniQure’s AAV5 gene therapies has experienced any confirmed cytotoxic T-cell-mediated immune response to the capsid. Additionally, pre-clinical and clinical data show that AAV5-based gene therapies may be viable treatments in patients with pre-existing antibodies to AAV5, thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates.

One of the major challenges in AAV-based gene therapy is the presence of circulating anti-AAV neutralizing antibodies, which can pre-exist in patients and may prevent successful gene transfer.  We have presented preclinical data demonstrating successful and effective transduction of AAV5 in non-human primates with pre-existing anti-AAV5 neutralizing antibodies (NABs).  At all observed levels, pre-existing neutralizing antibodies for AAV5 did not have a negative impact on the transduction effectiveness of the AAV5 vector. This suggests a much broader potential population of eligible patients than previously expected for AAV5-based gene therapies, as it appears that patients with pre-existing anti-AAV5 NABs may still be able to be successfully treated with AAV5 gene therapies.  

High levels of circulating anti-AAV neutralizing antibodies can develop after a single administration of gene therapy and can prevent successful gene transfer in patients.  We have made tremendous progress in optimizing and advancing re-administration and cross-administration protocols that we believe will significantly impact the application of our gene therapies and potentially enable repeated administration.  We have presented preclinical data demonstrating successful re-administration of gene therapy with our AAV5 vector following a proprietary immunoadsorption procedure in non-human primates (NHPs). In addition, we have published data demonstrating successful cross-administration of gene therapies in NHPs using sequential administration of AAV5 and AAV1 vector serotypes, suggesting that cross-administration of AAV5 gene therapies with other vectors may be possible in humans.

AAV5 is a highly differentiated, best-in-class vector with the potential to more effectively and safely deliver gene therapies to a greater portion of patients in need of treatment.

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Administration technologies to effectively deliver the relevant transgene into the liver or central nervous system 

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Administration technology

We and our collaborators are developing expertise in utilizing a variety of technologies to administer the vector to the body in order to optimize delivery of our gene therapies into tissues or organs relevant to the indication we are targeting. Administration technologies include intravenous infusion in our hemophilia B program or MRI-guided injection into the brain in our Huntington's disease program.

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Paired with our state-of-the-art manufacturing process, uniQure brings together all key elements for a successful gene therapy product.

The platform is designed to be modular, in that it may allow us to efficiently develop, manufacture and seek regulatory approval for multiple gene therapies generally using the same principal components. In some cases, we believe that the disease-specific gene cassette will be the only component that needs to be changed to target a new disease in a particular tissue. As a result, we may be able to reduce the overall preclinical and potentially clinical development activities required to obtain regulatory approval, and to significantly reduce the overall development risk, time and cost.

miQURE: An Advance in Gene Therapy Technology

uniQure's miQURE technology is our proprietary, next-generation gene silencing platform. It is designed to degrade disease-causing genes, without off-target toxicity, and induce silencing of the entire target organ through secondary exosome-mediated delivery. Gene therapy candidates designed with miQURE incorporate proprietary, therapeutic miRNA constructs that can be delivered using AAVs to potentially provide long-lasting activity. 

Preclinical studies of miQURE-based gene therapies have demonstrated several important advantages, including enhanced tissue-specificity, improved nuclear and cytoplasmic gene lowering and no off-target effects associated with impact to the cellular miRNA or mRNA transcriptome. miQURE technology has been incorporated in AMT-130, our investigational gene therapy for Huntington’s disease as well as in AMT-150 for SCA3

Learn more about uniQure's miQURE technology in the animation below: