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A tissue-specific promoter is active in only certain cell types which can restrict unwanted transgene expression. Tissue specific promoters are useful in gene therapy to ensure the safety of a gene-therapeutic drug for normal tissues. Many tissue-specific promoters have been identified and widely used for driving gene expression in specific types of cells or tissues such as neural cells, liver cells, muscle cells, astrocytes, etc.
Creative Biogene offers premade AAV particles that contain different tissue-specific promoters including neuron-specific promoters (synapsin, CaMKII), liver-specific promoters (TBG, ApoE/AAT1), muscle-specific promoters (tMCK, MHCK7), cardiac muscle-specific promoters (αMHC, cTNT), astrocyte-specific promoter GFAP.
Tissue-specific AAV vectors leverage regulatory elements, such as promoters, enhancers, or silencers, selectively active in specific cell types. Through promoter screening, the optimal one for restricted expression in the desired cell population is identified. This precision allows AAV cargo to target specific organs, cell lineages, or disease sites. For instance, a neuron-specific synapsin promoter prevents off-target gene expression. Capsid engineering enhances tropism for selective cell targeting. Inducible promoters, activated by exogenous factors, control timing. Creative Biogene's tissue-specific AAVs enable precise transgene expression, enhancing safety and performance in gene therapy.
Our products play a key role in research on:
Case Study 1
The bile acid (BA) nuclear receptor, farnesoid X receptor (FXR/NR1H4), maintains metabolic homeostasis by transcriptional control of numerous genes. Using liver-targeted AAV8 vectors, researchers demonstrated the importance of hepatic FXR phosphorylation by FGF15/19-Src signaling in regulating cholesterol homeostasis and atheroprotection. In mice with liver-specific FXR deletion then reconstitution, wildtype but not Y67F-FXR increased cholesterol efflux genes, reduced cholesterol, and protect against atherosclerosis. Knocking down Src impaired these effects. FXR activation by an agonist required FGF15. FGF19 increased FXR occupancy, target genes, and cholesterol efflux in hepatocytes in a Src and Y67-dependent manner.
Figure 1. For virus-mediated liver-specific down-regulation of FXR, AAV serotype 8 (AAV8) vectors containing a liver hepatocyte-specific TBG promoter were used. Mice were injected via the tail vein with 100 μl of a mixture of AAV-TBG-Cre and either AAV8-TBG-GFP, AAV8-TBG-FXR WT or AAV8-TBG-Y67F-FXR at 5×1010 virus particles/mouse. (Byun S, et al., 2019).
Case Study 2
Hepatocytes are replenished gradually during homeostasis and robustly after liver injury. In this study, researchers employed adeno-associated viruses (AAVs) expressing diphtheria toxin (DTA) to ablate Tert-expressing hepatocytes in mice. Coinfecting with AAV-Cre to induce DTA expression led to massive necrosis, while AAV-DTA alone did not. In Tert-CreERT2 mice, AAV-DTA reduced Tomato+ TERThigh cells by 75%. After ablating TERThigh cells, the DDC diet injured the liver. Compared to AAV-GFP controls, Tomato+ cell expansion was suppressed with AAV-DTA, leading to increased fibrosis, stellate cell activation, and ductal reaction. Replicating these results with an independent AAV-flex-DTA construct confirmed that hepatocyte-targeted AAV-DTA demonstrated TERThigh cells' crucial role in normal regeneration during DDC injury, with their ablation causing pathological responses, including fibrosis.
Figure 2. AAV8 vectors with liver-specific TBG promoters were produced for the study, including two copies of the α-1-microglobulin/bikunin precursor (AMBP) enhancer elements followed by the promoter of the SERPINA7 gene and a mini-intron. (Lin S, et al., 2018).
Q: What is the purpose of capsid engineering, and how does this technique optimize the performance of AAV particles?
A: Capsid engineering aims to improve the extracellular packaging of AAV particles to enhance infection efficiency in specific tissues. By optimizing the capsid, we can strengthen the interaction between AAV particles and target cells, thereby improving transduction efficiency and specificity.
Q: Is there a direct relationship between transduction efficiency and the promoters and capsid engineering used in AAV particles?
A: Yes, there is a direct relationship between transduction efficiency and the promoters and capsid engineering of AAV particles. Promoters directly influence gene expression levels, while capsid engineering affects the interaction of AAV with cell receptors. Both factors collectively impact transduction efficiency.
Q: How is time-controlled gene expression achieved with inducible promoters?
A: Inducible promoters respond to external stimuli (such as drugs or light) to regulate time-controlled gene expression. This approach provides researchers with precise control over the timing of gene expression, facilitating the study of dynamic changes in specific biological processes.
| Cat.No. | Product Name | Price |
|---|---|---|
| AAB0011 | Syn-FLEX-CaMPARI AAV (Serotype 9) | Inquiry |
| AAB0012 | Syn-CaMPARI AAV (Serotype 9) | Inquiry |
| AAB0015 | Syn-FLEX-jGCaMP7c AAV (Serotype 9) | Inquiry |
| AAB0016 | Syn-FLEX-jGCaMP7f AAV (Serotype 9) | Inquiry |
| AAB0017 | Syn-FLEX-jGCaMP7b AAV (Serotype 9) | Inquiry |
| AAB0018 | Syn-FLEX-GCaMP6s AAV (Serotype 9) | Inquiry |
| AAB0020 | Syn-FLEX-NES-jRCaMP1b AAV (Serotype 8) | Inquiry |
| AAB0021 | Syn-FLEX-NES-jRGECO1b AAV (Serotype 8) | Inquiry |
| AAB0022 | Syn-FLEX-NES-jRGECO1a AAV (Serotype 8) | Inquiry |
| AAB0024 | Syn-FLEX-NES-jRCaMP1a AAV (Serotype 8) | Inquiry |
| AAB0026 | Syn-FLEX-GCaMP6s AAV (Serotype 8) | Inquiry |
| AAB0027 | Syn-FLEX-GCaMP6m AAV (Serotype 8) | Inquiry |
| AAB0028 | Syn-FLEX-GCaMP6f AAV (Serotype 8) | Inquiry |
| AAB0029 | Syn-FLEX-CaMPARI AAV (Serotype 8) | Inquiry |
| AAB0030 | Syn-CaMPARI AAV (Serotype 8) | Inquiry |
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