Adeno-associated virus (AAV) has emerged as the leading platform for in vivo gene delivery, offering a safe and efficient means of transducing a wide range of target cells and tissues. At Protheragen, we specialize in leveraging the unique properties of AAV to develop next-generation gene therapies that address a diverse array of rare diseases.
AAV-based gene therapy development refers to the scientific and medical practice of utilizing adeno-associated virus (AAV) vectors to deliver therapeutic genes directly into human cells. AAVs are small, non-pathogenic viruses that have evolved into potent tools for gene therapy due to their ability to integrate into the host genome with minimal immunogenicity and high target specificity. This approach allows for the correction of genetic disorders by replacing, silencing, or editing faulty genes.
Fig.1 AAVs in gene replacement therapy. (Wang D., et al., 2019)
AAV vectors are engineered to carry specific genetic payloads, which are designed to treat a variety of diseases, including inherited monogenic disorders and certain acquired conditions. The development process involves meticulous design of the vector to ensure efficient transduction, minimal off-target effects, and sustained expression of the therapeutic gene.
The field of AAV-based gene therapy is rapidly advancing, with significant strides made in vector design, manufacturing, and clinical application. Two AAV-based therapeutics, Glybera and Luxturna, have received regulatory approval in Europe and the United States, respectively, marking a milestone in gene therapy development. Clinical trials are underway for a range of diseases, including hemophilia, muscular dystrophy, and various neurological disorders. The success of these trials has underscored the potential of AAV vectors in transforming the treatment paradigm for genetic diseases.
Table 1. A selection of ongoing rAAV interventional trials. (Marrone L., et al., 2022)
| Primary gene delivery target | Condition | AAv capsid | Transgene product | Strategy | Phase |
| Brain | AADC deficiency | AAV2 | AADC | Replacement | Phase I |
| AAV2 | AADC | Replacement | Phase II | ||
| Batten disease (CLN6) | AAV9 | CLN6 | Replacement | Phase I/II | |
| Parkinson disease | AAV2 | GDNF | Addition | Phase I | |
| AAV2 | Neurturin | Addition | Phase I/II | ||
| AAV2 | AADC | Addition | Phase I/II | ||
| AAV2 | AADC | Addition | Phase I | ||
| Spinal cord | SMA | AAV9 | SMN | Replacement | Phase III |
| Giant axonal neuropathy | AAV9 | GAN | Replacement | Phase I | |
| Eye | Achromatopsia | AAV2 | CNGB3 | Replacement | Phase I/II |
| AAV8 | CNGB3 | Replacement | Phase I/II | ||
| LCA | AAV2 | RPE65 | Replacement | Phase III | |
| AAV5 | RPE65 | Replacement | Phase I/II | ||
| LHON | AAV2 | ND4 | Replacement | Phase I | |
| AAV2 | ND4 | Replacement | Phase III | ||
| RP (RLBP1) | AAV8 | RLBP1 | Replacement | Phase I/II | |
| X-linked retinoschisis | AAV2 | RS1 | Replacement | Phase I/II | |
| AAV8 | RS1 | Replacement | Phase I/II | ||
| Liver | Crigler-Najjar syndrome | AAV8 | UGT1A1 | Replacement | Phase I/II |
| ND | UGT1A1 | Replacement | Phase I/II | ||
| FH (homozygous) | AAV8 | LDLR | Replacement | Phase I/II | |
| GSD1a | AAV8 | G6PC | Replacement | Phase I/II | |
| Haemophilia A | AAVhu.37 | FVIII | Replacement | Phase I/II | |
| AAV8 | FVIII | Replacement | Phase I/II | ||
| AAV5 | FVIII | Replacement | Phase III | ||
| Liver | Haemophilia B | AAV8 | FIX | Replacement | Phase I/II |
| AAV6 | FIX | Replacement | Phase I | ||
| ND | FIX | Replacement | Phase III | ||
| AAV5 | FIX | Replacement | Phase III | ||
| OTC deficiency | AAV8 | OTC | Replacement | Phase I/II | |
| Muscle | A1AT deficiency | AAV2 | A1AT | Replacement | Phase I |
| CMT1A | AAV1 | NTF3 | Addition | Phase I/II | |
| Pompe disease | AAV8 | GAA | Replacement | Phase I/II | |
| AAV9 | GAA | Replacement | Phase I | ||
| X-linked MTM | AAV8 | MTM1 | Replacement | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Protheragen is committed to advancing the field of gene therapy through our comprehensive AAV-based gene therapy development services, ensuring that our clients have access to the highest quality vectors and support throughout the development process.
AAV Vector Design and Optimization
We provide end-to-end support in the design and optimization of rAAV vectors, including the selection of appropriate promoters, transgene cassettes, and regulatory elements to ensure robust and sustained gene expression.
AAV Production and Purification
Leveraging our state-of-the-art GMP-compliant facilities and proprietary manufacturing platforms, we offer reliable and scalable AAV production and purification services to meet the diverse needs of our clients.
AAV Characterization and Quality Control
Our comprehensive analytical capabilities enable us to thoroughly characterize the physical, biochemical, and functional properties of our AAV products, ensuring consistent quality and safety for downstream applications.
Preclinical Evaluation and Validation
We conduct rigorous in vitro and in vivo studies to evaluate the efficacy, biodistribution, and safety of our AAV-based gene therapy candidates, providing valuable data to support clinical translation.
Gene Replacement
Protheragen utilizes AAV vectors to deliver a functional copy of the gene, effectively replacing the defective one.
Gene Silencing
For diseases caused by gain-of-function mutations, Protheragen employs RNA interference (RNAi) and other gene editing technologies to silence the problematic genes.
Gene Addition
This involves the delivery of genes that can supply missing or beneficial proteins, such as neurotrophic factors for neurological diseases or antibodies that neutralize infections.
Gene Editing
Using programmable nucleases, we aim to precisely correct genetic defects at the DNA level, offering a potential cure for a range of genetic disorders.
We leverage cutting-edge AAV vector platforms to offer a comprehensive suite of solutions for a variety of diseases to pharmaceutical companies worldwide. Our one-stop service portfolio encompasses diagnostic development, therapeutic research and development, disease model innovation, and preclinical research services, catering to the diverse needs of our global clientele.
Drawing on our extensive expertise, we can design and construct tailored AAV capsid libraries based on our client's specific requirements. This includes targeting particular cell types, species, or disease indications of interest. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
Our AAVLinkTM platform is at the forefront of adeno-associated viral (AAV) vector development, leveraging our extensive expertise and state-of-the-art technologies to drive innovation in gene therapy.
