Synthetic nucleic acids could be designed in sequence-specific structure to trigger endogenous repair systems. Depending on this concept, peptide nucleic acids (or PNAs) could achieve non-enzymatic gene editing i.e. without the use of nucleases unlike CRISPR and TALENs. PNAs could bind to the DNA to form highly specific hetero-triplex structures, so PNAs have been used severally in the last decades to induce correction of different human disease-causing mutations with low off-targets. Systemic in-vivo and in-utero application of PNAs had been enabled thanks to the advances in their chemical structure, design and delivery resulting in considerable preclinical editing in mouse models. Treated animal models engineered with a human beta globin gene (HBB gene carrying a β-thalassemia mutation, showed clinically considerable protein expression, suggesting that PNAs could have a curative potential for genetic disorders. The complete methods of design, preparation and evaluation of the PNA/DNA nanoparticles formulation will be discussed in details in addition to its use in cells treatment aiming for paving the road for interested scientists in gene editing techniques for treating different single gene disorders.