Gene augmentation is an attractive and viable approach in treatment of inherited diseases, despite its limitations, such as the eliciting of host immune response, and the sustainability of gene expression. Therefore, alternative therapeutic approaches are being investigated, such as the use of chimeric RNA-DNA oligonucleotides (chimeraplasts), in which a mutated allele that already exists in an affected individual can be corrected. Although the only gene defects that can be corrected by chimeraplasty are point mutations, and the correction frequencies are variable, it has been observed that intracellular delivery of oligonucleotides is likely to be more efficient than that of plasmid DNA or viral vectors. Furthermore, corrected genes are expressed from their autologous promoters, thus ensuring correct spatial and temporal expression. Here we report on the recent progress made in the field of chimeraplasty, and the problems encountered.