Liver-Specific DNase Expression for cfDNA Clearance

The patent uses a viral vector (AAV or adenovirus) as an intermediary delivery system to transport DNase gene into liver cells. This mediator enables targeted gene delivery to hepatocytes, allowing the DNase enzyme to be produced locally within the liver where cfDNA accumulates, thereby overcoming the limitation of systemic DNase administration that cannot effectively clear cfDNA from hepatic porto-sinusoidal circulation.

The liver cells are transformed into self-service factories that continuously produce and secrete DNase enzyme. By introducing the DNase gene into hepatocytes via viral vectors, the liver cells themselves generate the therapeutic enzyme locally, maintaining sustained high concentrations of DNase in the hepatic porto-sinusoidal circulation where it is most needed for cfDNA clearance, rather than relying on intermittent systemic administration.

The patent applies local quality by making the DNase expression liver-specific rather than systemic. Through using liver-targeted viral vectors and liver-specific promoters, the DNase gene is selectively expressed in hepatocytes, creating high local concentration of the enzyme precisely where cfDNA accumulates in the hepatic porto-sinusoidal circulation, maximizing therapeutic effect while minimizing off-target effects.

The patent utilizes parameter changes by modifying viral vector properties to achieve liver-specific targeting. Specific capsid proteins or mutations are employed to alter the tropism of viral vectors, directing them preferentially to liver cells. Additionally, liver-specific promoters regulate the expression level of DNase, creating optimal local concentration parameters in the liver while maintaining safety in other tissues.