Peptide Nucleic Acids (PNA) are oligonucleotide analogs widely used as antisense and antigene molecules thanks to their stability and affinity towards DNA and RNA targets. Since antisense PNAs, unlike oligonucleotides, do not recruit RNaseH upon binding to mRNA, they can be used to interfere in splicing events, and any time the RNase support is not required. There are several examples of aberrant splicing induced diseases, one of which is beta-thalassemia, a very common genetic disease due to mutations causing defective p globin gene expression, leading to a deficiency in haemoglobin A production. More than 100 thalassemic mutations have been identified so far, the most common being those causing aberrant splicing. These mutations are found in intron 1 and intron 2 of the (3 globin gene. In this work we investigated the effect of a 14-mer PNA (PNA110) targeting the IVS-110 region of the beta globin gene intron 1, where a G to A mutation is found. Furthermore, the 14-mer PNA was conjugated to the SV40 NLS peptide (PNA110/NLS) to enhance the PNA concentration in cells.
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