Next-generation AAV gene therapy from joined German forces

In vivo gene delivery was revolutionized by the introduction of AAV-based vectors, which have taken center stage in the development of gene therapies against a wide range of diseases with a genetic component. The tremendous potential of this versatile vector class is undisputed and illustrated by its growing presence in clinical gene therapy trials. While individual applications have already yielded promising results, culminating in the commercialization of two AAV vector-based gene therapies, recent reports from several trials project a growing need for vector optimization technologies to expand the range of AAV target cells and to improve vector and thus patient safety. With a major portion of the vector industry concentrating on questions of large-scale AAV production, there has been only little initiative to unify isolated talent and build a comprehensive, flexible technology platform that is accessible to the drug development industry.

With their new preferred partnership agreement in place, Heidelberg University Hospital’s Prof. Grimm and SIRION Biotech set a milestone for the AAV field, integrating commercial expertise for viral vectors and understanding of the needs of a fast-paced client base, with the newest scientific advances in AAV optimization. The undersigned partnership agreement will help compose consistent long-term projects while maintaining a maximum of flexibility. It enables users to access multiple engineering techniques that help to optimize vector cell and tissue specificities, to boost its productivity and to reduce vector immunogenicity. This will enable customers to obtain and use truly innovative vectors that go beyond the current state-of-the-art and that will be tailored to their specific demands, thereby increasing the customers‘ chances of success in clinical trials.

“Establishing a fixed cooperation agreement with Prof. Grimm and Heidelberg University Hospital will help us streamline the way we plan and implement our AAV engineering collaborations. Our industrial partners will be able to enter clinical trials months earlier than previously possible, with capsids and vectors optimized for their specified goals,” says Dr. Christian Thirion, CEO and founder of SIRION Biotech GmbH. “This collaboration with Prof. Grimm offers our customers direct access to the very latest AAV technologies, to maximize the efficiency and safety of their gene therapy programs”, adds Dr. Sabine Ott, VP Business Development & Licensing.

Dr. Dirk Grimm, Professor for Viral Vector Technologies at Heidelberg University Hospital explains: “This preferred partnership agreement underpins our long-lasting fruitful collaboration with SIRION and accelerates our efforts to leverage our expertise in AAV capsid optimization toward the clinic for a variety of disorders“.

SIRION Biotech specializes in custom engineering services for viral vectors in the life sciences and industry. The Germany-based technology expert can cover small- to large-scale projects for customers all around the globe. SIRION‘s unique focus on gene delivery aspects enables it to master broad customization and engineering projects for all 3 major virus systems (AAV, adenovirus, lentivirus [LV]), for therapeutic and research purposes. The company has a strong customer base in cancer research, neurosciences, regenerative medicine, gene therapy and immuno-oncology. Further advances in the gene therapy space are projected with the development and licensing of clinically applicable LV transduction enhancers and the expansion of its strategic and collaborative network in AAV technology.

With this new alliance of SIRION Biotech and its recently announced partnership with Vibalogics GmbH to harmonize pre-clinical production methods with GMP-production processes, SIRION Biotech offers to its industrial customers to set-up, process and coordinate the entire spectrum from AAV engineering until manufacturing of the optimized AAV candidates under GMP conditions.

Prof. Grimm is an expert in AAV vector design and engineering who pioneered the use of molecular evolution technologies for generation of AAV capsids with altered cell specificities and other improved properties. Located in the BioQuant building in the center of the Heidelberg University life sciences campus, his large team of scientists and technicians exploits these technologies to create novel AAV vectors for human gene therapies of diseases such as infection with viral or parasital pathogens, or of monogenic disorders affecting major organs such as skeletal muscle, heart or lung. In addition, the Grimm laboratory possesses fundamental expertise in the customization of AAV vector genomes for in vitro and in vivo expression of cDNAs, DNA engineering (CRISPR), gene knockdown (RNAi) and cellular reprogramming molecules. This is documented in ~80 peer-reviewed publications, many of which appeared in high-profile journals such as Nature, Nature Structural & Molecular Biology, Nature Communications, Journal of Clinical Investigation, PNAS, Nucleic Acids Research or EMBO Molecular Medicine. Besides, Prof. Grimm is an integral member of several comprehensive and international research consortia such as the EU H2020 program MYOCURE, in which he and his team essentially contribute to the preclinical and clinical development of novel AAV-based human gene therapies.

Heidelberg University Hospital and Medical Faculty: Heidelberg University Hospital is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University belongs to the internationally most renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. With about 13,000 employees, training and qualification is an important task. Every year, around 65,000 patients are treated on an inpatient basis, 56,000 cases on a day patient basis and more than 1,000,000 cases on an outpatient basis in more than 50 clinics and departments with almost 2,000 beds. Together with the German Cancer Research Center (DKFZ) and German Cancer Aid, Heidelberg University Hospital has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic.