Adeno-Associated Viral Vector Development Platform
Adeno-associated virus (AAV) is a non-enveloped virus that can transport DNA to target cells through genetic engineering, and it has garnered significant attention in the field of gene therapy. Our company aims to better understand AAV vector gene delivery and activation of gene expression to help customers develop AAV vectors for gene therapy of rare diseases. Our improved vector manufacturing and efficiency for AAV gene therapy bring superior quality to the rapidly growing gene therapy market.
Introduction to Adeno-associated Viral Vectors
Adeno-associated virus (AAV) is a protein shell that surrounds and protects a small, single-stranded DNA genome of approximately 4.8kb. Its single-stranded genome contains three genes: Rep (replication), Cap (capsid), and AAP (assembly). The discovery of DNA as the biological molecule responsible for genetic inheritance and diseases has opened up prospects for improving human conditions by altering mutated genes. Many viral vectors can be chosen to deliver the target nucleic acid (DNA or RNA) into host cells for replication. Each of them has some unique properties, and adenovirus-associated vectors are currently one of the most active gene therapy vectors under research.
Fig.1 Protocol of rAAV production. (Fernandez-Sendin, M., et al., 2020)
Adeno-associated Virus Transfer in Cell and Release of Carry-On Item
In recombinant AAV (rAAV) vectors used for gene therapy, natural coding, and non-coding viral genes are replaced by a transgenic cassette with a total coding capacity of approximately 4.7 kb. This cassette is integrated between the inverted terminal repeats (ITR) and typically includes tissue-specific or ubiquitously present promoters, transgene sequences, and polyadenylation (polyA) signals.
Adeno-associated Viral Vectors for Rare Diseases
The mainstream gene delivery method is virus-mediated delivery, and currently, among viral vectors, AAV (Adeno-Associated Virus) is the most widely used delivery vector in vivo gene therapy applications due to its excellent tissue specificity, low immunogenicity, and high safety. Gene therapy using AAV as the vector primarily targets the eye, brain, muscles, and liver. Research has shown that AAV gene therapy can treat some rare diseases.
Table 1 Application of AAV serotypes in rare diseases. (Li, Chengwen, and R. Jude Samulski., 2020)
| AAV serotype | Origin of isolation | Primary receptor | Co-receptor | Tissue tropism | Condition | Approved drug |
|---|---|---|---|---|---|---|
| AAV1 | Monkey | Sialic acid | AAVR | Muscle, CNS, heart | AAT deficiency (NCT01054339, NCT00430768) |
None |
| AAV2 | Human | Heparin | Integrin, FGFR, HGFR, LamR, AAVR | Liver, CNS, muscle | Haemophilia (NCT00515710) | Luxturna for Leber congenital amaurosis |
Our Services
Our company provides customers with recombinant and modified AAV vectors that have different serotypes to selectively deliver specific genes to different locations in the body. We develop and select the most suitable viral vector, including vector evaluation services, for the specific disease pathology profile based on our customers' rare disease drug discovery programs. The services we provide include but are not limited to:
- AAV Vectors Design
Providing AAV vector design services based on our advanced technology and professional team. Including but not limited to:
- Complementation system design
- AAV capsid selection and optimization
- Target gene integration
- Sequencing
- AAV Vectors Production
The following production platforms have been built to help our customers produce AAV vectors:
- HEK293 cells transfection with an adenovirus helper plasmid, an AAV helper plasmid, and an AAV vector plasmid.
- Mammalian stable cell lines
- Baculovirus/Sf9
- AAV Vectors Purification
Using the following techniques for purifying AAV to obtain an AAV product of high purity:
- A Two-column purification method combining affinity chromatography and ion exchange chromatography
- Density gradient centrifugation
- Chromatography purification
Project Workflow
With extensive experience in rare disease therapy research and development, our company provides customers with a convenient solution. Our adeno-associated viral vector development service is a simplified workflow by a group of specially trained and professional scientists. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Fernandez-Sendin, M., et al. "Production and use of adeno-associated virus vectors as tools for cancer immunotherapy." Methods in Enzymology 635 (2020): 185-203.
- Li, Chengwen, and R. Jude Samulski. "Engineering adeno-associated virus vectors for gene therapy." Nature Reviews Genetics 21.4 (2020): 255-272.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
