Truncated PAH Lentiviral Vector for PKU Gene Therapy

The patent replaces the mechanical/dietary restriction system with a biological/genetic system. Instead of relying on lifelong dietary avoidance, the invention uses lentiviral vectors to deliver functional PAH gene sequences to hepatic cells, enabling the liver to naturally metabolize phenylalanine. This substitution eliminates the burden of dietary restriction while maintaining phenylalanine control through enzymatic action.

The patent implements self-service by enabling the patient's own liver to produce functional PAH enzyme through viral vector delivery. The endogenous hepatic cells take over the metabolic function that previously required external dietary control, allowing the body to self-regulate phenylalanine levels without continuous external intervention or restriction.

The patent changes the fundamental parameter of treatment approach from supplementing a cofactor (BH4) to delivering the enzymatic protein itself (PAH gene). This parameter change expands effectiveness from 20-30% of patients to potentially all PKU patients, as it directly addresses the enzymatic deficiency rather than relying on cofactor availability and regulation.

The patent substitutes the biochemical supplementation approach (BH4) with a genetic therapy approach (PAH gene delivery). This replacement eliminates the limitations of cofactor-based therapy by directly providing the functional enzyme, thereby improving both effectiveness and adaptability across different patient populations.