26.1 Introduction:

Chimeraplasty is defined as the technique of synthetically creating a hybrid molecule consisting of both RNA and DNA and is being explored as a non viral method for gene therapy. It works in both plants as well as animals. RNA-DNA chimera is used to repair point mutations, deletions, or insertions in DNA. It is used for targeted gene correction.

Dr. Eric Kmiec began with the idea of chimeraplasty while studying homologous recombination where he observed an enhanced recombination rate during transcription. He realized that stability of RNA inside a cell could be increased when coupled with DNA and this RNA/DNA hybrid could be used to invoke gene repair by the endogenous repair mechanism of the cell. His first study was based on producing an oncogenic mutation in ras gene by changing thymine to guanine at a critical segment. The chimera he designed consisted of 25 bases of which a 5 bases DNA segment was flanked by two segments of 10 bases RNA. Kyonggeun Yoon in her study corrected point mutation using chimeraplasty in the human alkaline phosphatase gene introduced in CHO cells with efficiency up to 30%. Yoon showed that RNA/DNA chimera was capable of introducing as well as correcting mutation. Later on Kmiec, Yoon, Allyson Cole-Strauss conducted experiments to treat sickle cell anaemia caused by a point mutation. From then onwards a lot of experiments have been conducted some with success and some with failure thus putting a question over the efficacy and limitations of this technology.