SmartEnzymes™ for 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 as transporters of new genetic material. Up to 60% of patients may have antibodies against this viral vehicle and this is usually an exclusion criteria for being eligible for gene therapy. To overcome the presence of neutralizing antibodies, a new strategy includes the use of highly specific IgG proteases to digest the antibody population and increase the uptake of the new genetic material.
Genovis offers a range of IgG-specific proteases including FabRICATOR® (IdeS), FabRICATOR® Z (IdeZ) and the recently discovered Xork™ protease. These enzymes digest IgG 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 for as pre-treatment to gene therapy administration. The results indicate a reduction in the anti-AAV antibodies and a correlating increased transduction of new genetic material (Leborgne et al. 2020, Elmore et al 2020).
Next week, Genovis will present at poster at the annual meeting of the American Society of Gene and Cell Therapy in Washington DC, USA. The poster is focused on characterization of the IgG proteases and their use as a pre-treatment for gene therapies, and has the title:
“Enzymatic Strategies for Eliminating Neutralizing Antibodies Prior to Administration of AAV Based Gene Therapies”
Session Date/Time: Tuesday May 17, 2022 5:30 PM – 6:30 PM
Poster Board Number: Tu-223
Session Title: Immunological Aspects of Gene Therapy and Vaccines I
Room: Hall D
Final abstract number: 718
For details on the SmartEnzymes for Gene Therapy, please contact Jonathan Sjögren, VP Business Development, jonathan.sjogren@genovis.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