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Introducing New AAV Serotypes: Expanding Possibilities in Gene Delivery
Published On 06/19/2024 6:24 PM
Overview
Adeno-associated viruses (AAVs) have revolutionized gene delivery, offering a safe and efficient way to introduce genetic material into target cells. As researchers and clinicians continue to explore AAV-based therapies, it’s essential to stay informed about the latest advancements. In this blog post, we’ll introduce the new AAV serotypes now available for purchase on our company website. Explore our wide selection of over 1,000 pre-made AAVs, available in 22+ different serotypes to meet your experimental needs.
See What New Serotypes Are Now Available From Biohippo
AAV2/B10
- AAV2/B10 is designed to cross the blood-brain barrier (BBB) after intravenous (IV) administration in mice. It is highly specific for neurons in the CNS, significantly decreased in all peripheral organs assayed and targeted away from the liver in mice.
- Comparison with AAV9: AAV9 is one of the natural serotypes that can cross the BBB but has low transduction efficiency in the brain and high off-target expression in the liver when administered intravenously. AAV-B10 achieves brain-wide transduction while significantly decreasing liver DNA and RNA levels compared to AAV9
AAV2/olig001
- AAV2/olig001 shows preferential transduction of oligodendrocytes, making it valuable for neuroscience and myelin-related studies. Explore AAV2/olig001 for investigating demyelinating diseases and developing targeted therapies.
AAV2/6.2FF
- AAV6.2FF is a rationally designed triple mutant adeno-associated virus (AAV) capsid. It was engineered to enhance gene delivery to specific tissues, particularly the lung epithelial cells (Kang et al., 2020). Its enhanced stability and binding characteristics make it a promising candidate for therapeutic applications (Thomas et al., 2024).
AAV2/BI30
- AAV-BI30 demonstrates a remarkable ability to specifically infect and transduce endothelial cells in the central nervous system. It achieves stable expression in both mouse and rat models, as well as in human microvascular endothelial cells in vitro. AAV-BI30 is based on the AAV9 capsid, with specific modifications. It contains a 7-mer insertion between amino acids 588 and 589 of the VP1 protein. Additionally, it carries the K449R mutation and an NNSTRGG insertion at the same location.
AAV2/7m8
- AAV2.7m8 is a versatile viral vector with promising applications in both inner ear disorders and retinal diseases.
- AAV2.7m8 has been successfully used to deliver gene therapy for improving auditory function in mouse models of hereditary hearing loss (Isgrig et al., 2019).
- It efficiently infects both inner hair cells (IHCs) and outer hair cells (OHCs) in the cochlea.
- Additionally, AAV2.7m8 targets inner pillar cells and inner phalangeal cells with high efficiency. This makes AAV2.7m8 an excellent candidate for inner ear gene therapy targeting cochlear hair cells and supporting cells.
- AAV2.7m8 has also been explored for retinal gene therapy. In clinical trials, it is known as ADVM-022 (AAV.7m8-aflibercept). ADVM-022 is used for the treatment of neovascular (wet) age-related macular degeneration (wet AMD) and Diabetic Macular Edema (DME)23. It offers the potential for sustained intraocular expression of aflibercept following a single intravitreal injection.
AAV2/BR1
- AAV-BR1 specifically delivers genes to retinal endothelial cells. It has been designed to reveal the morphological diversity of these cells.By using a GFP reporter, researchers identified distinct classes of ECs along the retinal vascular tree. This selective targeting is crucial for understanding and manipulating ECs in the CNS (Krolak et al., 2022).
- The AAV-BR1 system was further utilized to express ectopic Connexin 43 (Cx43) in ECs. Cx43 is a protein involved in gap junctions, which plays a role in cell communication. Loss of Cx43 has been implicated in microvascular impairments seen in diseases like diabetic retinopathy and vascular edema. Ectopic Cx43 expression was achieved using AAV-BR1-CAG-DIO-Cx43-P2A-DsRed2 in combination with a mouse line carrying inducible CreERT2 in ECs1 (Ivanova et al., 2021).
- Potential Therapeutic Applications: Enhancing gap junctions in ECs using AAV-BR1 provides a precise tool to treat microcirculation deficits. Microcirculation deficits are an early pathology observed in various diseases. AAV-BR1’s ability to specifically target retinal ECs makes it promising for therapeutic interventions.
AAV2/6m
- AAV2/6m is an engineered adeno-associated virus (AAV) serotype that has been designed for targeted gene delivery in the context of glaucoma research. Glaucoma is a neurodegenerative disease characterized by the progressive degeneration and eventual death of retinal ganglion cells (RGCs).
- AAV2/6m is associated with the Nuclear factor erythroid 2-Related Factor 2 (NRF2) pathway. NRF2 is a transcription factor that binds to the antioxidant response element (ARE) and increases transcription of antioxidant genes. In glaucoma, elevated intraocular pressure (IOP) triggers an endogenous antioxidant response mediated by NRF2.
- Researchers have used AAV2/6m to alter NRF2 levels in specific cell types. AAV2/6m expressing Cre recombinase was injected into either retinal ganglion cells (RGCs) or glial cells. Knocking down NRF2 in either cell type blunted the antioxidant response and resulted in earlier pathology and vision loss (Naguib et al., 2023).
- In summary, AAV2/6m is a valuable tool for investigating antioxidant responses and potential therapeutic interventions in glaucoma. Its ability to modulate NRF2-mediated pathways highlights its relevance in protecting retinal ganglion cells.
AAV2/MG1.2
- AAV-MG1.2 is an engineered adeno-associated virus (AAV) serotype that has been specifically designed for targeted gene delivery to microglia. AAV-MG1.2 enables in vivo two-photon imaging of microglia extracellular ATP changes following acute laser ablation. Importantly, it allows for microglia-specific gene knockout in vivo.
- The delivery of an sgRNA targeting the steady-state marker gene P2ry12 of microglia using AAV-MG1.2 effectively induces knockout and corresponding phenotypic changes (Zheng et al., 2023).
- In summary, AAV-MG1.2 provides a valuable tool for investigating microglia function, neuroinflammation, and potential therapeutic interventions.
AAV1/2
- The AAV1/2 vector is engineered to express both AAV1 and AAV2 capsid proteins on the viral surface. It combines the properties of AAV1 and AAV2, allowing it to infect a broader range of cells. It can be used to specifically target oligodendrocytes.
AAV2/MaCPNS1 and AAV2/MaCPNS2
- Peripheral nervous system of rodents (mice and rats), central and peripheral nervous system of non-human primates (rhesus macaques and marmosets)
- Notably, AAV2/MaCPNS2 is slightly more effective than AAV2/MaCPNS1 at transducing neurons and astrocytes in the brain.
Full List of AAV Serotypes Available at Biohippo
| AAV Serotype | Tissue Tropism |
|---|---|
| AAV2/1 | CNS (high-titer anterograde transsynaptic), skeletal muscle, cardiac muscle, smooth muscle, retina, vascular endothelial cells |
| AAV2/5 | Central nervous system, lungs, retina, liver, synovial joints, smooth muscle |
| AAV2/8 | Central nervous system, liver, kidney, muscle, adipose tissue, pancreas, retina |
| AAV2/9 | Central nervous system, cardiac muscle, retina, skin, lungs |
| AAV2/DJ | Retina, lungs, kidney, liver, in vitro infected cells |
| AAV2/RETRO | Nervous system (retrograde, non-transsynaptic) |
| AAV2/PHP.eB | Blood-brain barrier crossing |
| AAV2/2 | Retina, central nervous system, liver, vascular smooth muscle, skin, inner ear tissues, kidney |
| AAV2/6 | Nervous system, lungs, muscle, heart |
| AAV2/rh10 | Lungs, liver, heart central nervous system, blood, in vitro infected cells |
| AAV2/anc80L65 | Inner ear, retina, skeletal muscle, liver |
| AAV2/B10 | Blood-brain barrier crossing |
| AAV2/olig001 | Oligodendrocytes |
| AAV2/6.2FF | Lungs |
| AAV2/BI30 | Vascular endothelial cells |
| AAV2/7m8 | Retina |
| AAV2/BR1 | Brain microvascular endothelial cells |
| AAV2/6m | Microglia |
| AAV2/MG1.2 | Microglia |
| AAV1/2 | Oligodendrocytes |
| AAV2/MaCPNS1/ AAV2/MaCPNS2 | Peripheral nervous system of rodents (mice and rats), central and peripheral nervous system of non-human primates (rhesus macaques and marmosets) |
References:
1. Isgrig, K., McDougald, D.S., Zhu, J. et al. AAV2.7m8 is a powerful viral vector for inner ear gene therapy. Nat Commun 10, 427 (2019). https://doi.org/10.1038/s41467-018-08243-1
2. Ivanova, E., Corona, C., Eleftheriou, C. G., Stout, R. F., Körbelin, J., & Sagdullaev, B. T. AAV-BR1 targets endothelial cells in the retina to reveal their morphological diversity and to deliver Cx43. Journal of Comparative Neurology, 530(8), 1302–1317 (2022). https://doi.org/10.1002/cne.25277
3. Kang, M.H., van Lieshout, L.P., Xu, L. et al. A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency. Nat Commun 11, 3929 (2020). https://doi.org/10.1038/s41467-020-17577-8
4. Krolak, Trevor et al. A High-Efficiency AAV for Endothelial Cell Transduction Throughout the Central Nervous System. Nature cardiovascular research 1 (2022): 389 - 400.
5. Naguib, S., Backstrom, J.R., Artis, E. et al. NRF2/ARE mediated antioxidant response to glaucoma: role of glia and retinal ganglion cells. acta neuropathol commun 11, 171 (2023). https://doi.org/10.1186/s40478-023-01663-1
6. Sun, J., Zheng, Y. & Hu, J. Targeting Microglia with Adeno-associated Viruses. Neurosci. Bull. 39, 863–865 (2023). https://doi.org/10.1007/s12264-022-00975-x
7. Thomas, S.P., Spinelli, M.M., Rghei, A.D. et al. Analysis of the impact of pluronic acid on the thermal stability and infectivity of AAV6.2FF. BMC Biotechnol 24, 22 (2024). https://doi.org/10.1186/s12896-024-00853-6
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