Short tandem repeat (STR) RNAs play a pivotal role in the pathology of STR expansion-associated disorders. However, disease-related STR sequences are often GC-rich (>
66% GC), which makes sample preparation and detection challenging. GC-rich STR RNAs, particularly those composed entirely of GC (100% GC), frequently cause interruptions during reverse transcription. Additionally, the GC-rich STR DNA sequences generate low-yield and heterogeneous products when amplified via polymerase chain reaction. The lack of robust processivity of polymerases for GC-only STR poses major challenges in preparing samples and detecting such sequences with physiologically relevant lengths. Herein, we report the