Patient-specific mutant RNA sequence

A patient-specific mutant RNA sequence refers to a unique ribonucleic acid transcript containing a mutation found only in an individual patient or a very small subset of patients. These sequences serve as highly specific therapeutic targets in the field of personalized medicine, particularly for N-of-1 therapies and neoantigen-based cancer vaccines (Kim et al., 2019, NEJM). In rare genetic diseases, antisense oligonucleotides (ASOs) can be custom-designed to bind to these unique sequences to correct splicing errors or suppress toxic gain-of-function transcripts, as demonstrated by the development of Milasen for a specific CLN7 mutation. In oncology, patient-specific mutant mRNAs are identified through genomic sequencing of a patient's tumor and used to create personalized vaccines that train the immune system to recognize the resulting neoantigens (Sahin et al., 2017, Nature). This target class represents a paradigm shift from traditional drug development toward treatments tailored to the unique molecular signature of a single patient's disease (Weber et al., 2024, Lancet). However, the approach requires rapid, individualized manufacturing and sophisticated bioinformatics to ensure target specificity and safety.

Other names

Personalized mutant RNANeoantigen-encoding RNAPatient-specific transcriptUnique mutant mRNAN-of-1 RNA target

Targeting of unique sequences via antisense oligonucleotides (ASOs) for splice modulation or degradation, or use as a template in personalized mRNA vaccines to induce immune responses against neoantigens.