Promoters are sequences of DNA that control where and when genes are expressed. They serve as landing pads for the cellular machinery that carries out transcription, the process of making an RNA copy of a gene. By choosing different promoters, researchers can control the spatial and temporal expression of a transgene, the gene that is being introduced into the cells.
Liver-specific promoters are sequences of DNA that are recognized by the transcription machinery primarily or exclusively in liver cells. When a liver-specific promoter is used in gene therapy, it ensures that the therapeutic gene is expressed predominantly in the liver, reducing off-target gene expression in other tissues. This can improve the safety and efficacy of the therapy.
Some examples of liver-specific promoters include:
- Albumin promoter: The albumin gene is highly expressed in the liver, and its promoter is often used to drive liver-specific expression of transgenes.
- Alpha-1 antitrypsin (AAT) promoter: The AAT gene is primarily expressed in the liver, and its promoter can be used to achieve liver-specific expression.
- Transthyretin (TTR) promoter: The TTR gene is expressed in the liver and the choroid plexus in the brain, and its promoter can be used to target these tissues.
- Apolipoprotein E (ApoE) promoter: The ApoE gene is expressed in the liver and macrophages, and its promoter can be used to target these cells.
In addition to these, synthetic or hybrid promoters have been designed to achieve robust and liver-specific expression of transgenes. These promoters combine elements from different promoters to optimize their activity.
The use of liver-specific promoters in liver transfection allows for targeted and efficient gene expression in the liver, reducing potential side effects in other tissues. However, one challenge is that these promoters can be quite large, which can be a limitation for viral vectors with a small cargo capacity, like adeno-associated virus (AAV). As such, research is ongoing to develop smaller, liver-specific promoters that can fit into these vectors.