Tripeptidyl-peptidase 1 (TPP1) mRNA (TPP1 mRNA)

Tripeptidyl-peptidase 1 (TPP1) mRNA is the transcript of the TPP1 gene, which encodes a lysosomal serine protease essential for the catabolism of polypeptides into tripeptides (UniProt P20648). Mutations in this mRNA, particularly those leading to mis-splicing or premature termination, result in a deficiency of the TPP1 enzyme, causing Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a fatal neurodegenerative lysosomal storage disorder (NIH GARD). TPP1 mRNA has emerged as a therapeutic target for antisense oligonucleotides (ASOs) designed to correct genetic defects at the transcript level. A landmark example is Milasen, a custom-designed ASO that targets a cryptic splice site in the TPP1 pre-mRNA to restore functional protein production in a patient with a unique mutation (Kim et al., N Engl J Med, 2019). By modulating mRNA processing, these therapies aim to address the underlying cause of neurodegeneration rather than relying solely on enzyme replacement. Therapeutic challenges include ensuring efficient delivery across the blood-brain barrier and minimizing off-target hybridization effects.

Other names

CLN2 mRNATripeptidyl aminopeptidase 1 mRNATPP-I mRNAGSU mRNA

Splice-switching antisense oligonucleotide (ASO) binding to pre-mRNA to restore correct splicing and functional protein expression.