Mammalian cloning: advances and limitations

For many years, researchers cloning mammals experienced little success, but recent advances have led to the successful cloning of several mammalian species. However, cloning by the transfer of nuclei from adult cells is still a hit-and-miss procedure, and it is not clear what technical and biological factors underlie this. Our understanding of the molecular basis of reprogramming remains extremely limited and affects experimental approaches towards increasing the success rate of cloning. Given the future practical benefits that cloning can offer, the time has come to address what should be done to resolve this problem. Key Points Several mammalian species have been cloned by transferring nuclei from various adult somatic cells into enucleated oocytes. The cloning procedure is still inefficient, and only one in a hundred of manipulated oocytes develop to adulthood. Reasons for the low efficiency of cloning are largely unknown and are probably both technical and biological. The incomplete or incorrect reprogramming of the donor nuclear genome — its inability to completely adapt and function in the new environment — is the most significant factor contributing to low cloning efficiency. The cloning of large farm animals from genetically manipulated donor nuclei will have significant practical benefits. The cloning of humans is prohibited because of safety reasons at present. However, therapeutic cloning and the production of individualized human embryonic stem cells for use in cell- and tissue-replacement therapies may have great importance in human medicine.