SmartEnzymes for Gene Therapy
Reduce Neutralizing Antibodies
Genovis provides highly specific IgG proteases to reduce neutralizing antibodies prior to gene therapy administration, to expand the patient eligibility for gene therapies.
Why SmartEnzymes™ for Gene Therapy?
- Our unique IgG proteases reduce neutralizing antibodies and may increase successful gene therapy administration
- The IgG proteases are recombinantly produced
- All IgG proteases are purified to the highest standards with validated and controlled low endotoxin levels to enable in vivo applications
1. Viral vector (AAV) carrying a healthy gene to be transferred to a patient.
2. Pre-existing antibodies recognize the virus carrying the genetic material as foreign. The virus is neutralized and the genetic material is prevented from being transferred to the patient.
3. Our unique IgG proteases effectively eliminiate neutralizing antibodies by specific digestion and clearance of IgG.
4. When administered prior to gene therapy, the IgG proteases may increase the successful transduction of healthy genetic material to the patient.
IgG Proteases and Neutralizing Antibodies in Gene Therapy
The development of advanced gene therapies is promising and gives thousands of patients new hope for a curative treatment. However, many of the current gene therapies are using adeno-associated viruses (AAV) as transporters of the new genetic material. Up to 60% of patients may have antibodies against this viral vehicle, and the presence of such neutralizing antibodies is usually an exclusion criteria for being eligible for gene therapy. A new strategy to avoid the problem of neutralizing antibodies includes the use of highly specific IgG proteases to digest the antibody pool, increase the clearance of the antibodies and hence increase the uptake of the new genetic material.
Unique IgG Specific Proteases from Genovis
Genovis offers a range of IgG-specific proteases including FabRICATOR® (IdeS), FabRICATOR® Z (IdeZ) and the recently discovered Xork™ protease. These enzymes digest the neutralizing antibodies below the hinge, generating F(ab’)2 and Fc fragments that result in increased clearance of the antibodies. Recently, several publications have highlighted the use of IdeS or IdeZ as pre-treatment to gene therapy administration. The results indicate a reduction in the anti-AAV antibodies and a correlating increased transduction of the new genetic material (Leborgne et al. 2020, Elmore et al 2020). FabRICATOR, FabRICATOR Z and Xork are available from Genovis in a Preclinical Grade format with low endotoxin levels for the use in gene therapy evaluation studies.
Xork™ – New Protease with Unique Features
FabRICATOR is derived from group A Streptococcus, a human pathogen that commonly infect humans and may cause diseases such as strep throat. Since the human population is exposed to the enzyme, antibodies against the enzyme are prevalent and affect the ability of this enzyme to reduce neutralizing antibodies prior to gene therapy. The Xork enzyme is a newly discovered enzyme developed from a non-human pathogen that displays the same human IgG-digesting ability as FabRICATOR. However, since no pre-existing antibodies are present towards this enzyme, the potential of successful transduction is increased, and new gene therapies could be made available to a larger number of patients.
Available Products
| Product Name | Product ID | Request a Quote |
|---|---|---|
| FabRICATOR Preclinical Grade 1 mg [1 mg/ml] | A0-FR8-101 | Contact us |
| FabRICATOR Preclinical Grade 1 mg [5 mg/ml] | A0-FR8-105 | Contact us |
| FabRICATOR Z Preclinical Grade 1 mg [1 mg/ml] | A0-FZ8-101 | Contact us |
| FabRICATOR Z Preclinical Grade 1 mg [5 mg/ml] | A0-FZ8-105 | Contact us |
| Xork Preclinical Grade 1 mg [1 mg/ml] | A0-XR8-101 | Contact us |
| Xork Preclinical Grade 1 mg [5 mg/ml] | A0-XR8-105 | Contact us |
Affinity Reagents for IgG Proteases
Genovis offers affinity reagents to detect residual enzyme levels in complex samples. Goat polyclonal antibodies detecting the enzymes are available for the FabRICATOR (IdeS), FabRICATOR (IdeZ) and Xork enzymes. The antibodies can be used to detect the enzymes in Western blot and ELISA assays, as well as in preclinical gene therapy applications.
Available Products
| Product Name | Product ID | Order Product |
|---|---|---|
| Anti-FabRICATOR Affinity Purified 0.1 ml [1 mg/ml] | A3-AF2-010 | Read more and Order |
| Anti-FabRICATOR Affinity Purified Biotin Conjugated 0.1 ml [0.5 mg/ml] | A3-AF3-005 | Read more and Order |
| Anti-FabRICATOR Protein G Purified 0.1 ml [4 mg/ml] | A3-AF1-010 | Read more and Order |
| Anti-FabRICATOR Z Affinity Purified 0.1 ml [1 mg/ml] | A3-AZ2-010 | Read more and Order |
| Anti-FabRICATOR Z Affinity Purified Biotin Conjugated 0.1 ml [0.5 mg/ml] | A3-AZ3-005 | Read more and Order |
| Anti-Xork Affinity Purified 0.1 ml [1 mg/ml] | A3-AX2-010 | Contact us |
| Anti-Xork Affinity Purified Biotin Conjugated 0.1 ml [0.5 mg/ml] | A3-AX3-005 | Contact us |
The antibodies are qualified for the use of e.g., western blot and ELISA to detect the FabRICATOR Z enzyme. Here, we show the performance of both Anti-FabRICATOR Z Affinity Purified as well as Anti-FabRICATOR Z Affinity Purified Biotin conjugated.
The wells were coated with Anti-FabRICATOR Z Affinity Purified at 2 μg/ml. The FabRICATOR Z enzyme was added in dilutions from 2 μg/ml to 2 ng/ml. Anti-FabRICATOR Z Affinity Purified Biotin Conjugated was added at 1 μg/ml. HRP-Streptavidin was added in a 1:2000 dilution.
Contact Us
Would you like to receive a quote, or do you have any questions about our IgG Proteases for Gene Therapy? Contact us here!
Partnership with Selecta Biosciences
The enzymes are available for preclinical use and Xork is available for preclinical use through Genovis and for clinical use through our partnership with Selecta Biosciences (Learn more). To learn more about the path to the clinic, please contact our business development team at bd@genovis.com.
About Selecta Biosciences
Selecta Biosciences Inc. (NASDAQ: SELB) is a clinical stage biotechnology company leveraging its ImmTOR® platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses. With a proven ability to induce tolerance to highly immunogenic proteins, ImmTOR has the potential to amplify the efficacy of biologic therapies, including re-dosing of life-saving gene therapies, as well as restoring the body’s natural self-tolerance in autoimmune diseases. Selecta has several proprietary and partnered programs in its pipeline focused on enzyme therapies, gene therapies, and autoimmune diseases. Selecta Biosciences is headquartered in the Greater Boston area. For more information, please visit www.selectabio.com.
References
Leborgne, C., Barbon, E., Alexander, J.M. et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med 26, 1096–1101 (2020). https://doi.org/10.1038/s41591-020-0911-7
Elmore ZC, Oh DK, Simon KE, Fanous MM, Asokan A. Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme. JCI Insight. 2020 Sep 17;5(19):e139881. doi: 10.1172/jci.insight.139881