Cloning challenges, current and future applications

More than two decades have passed since Dolly the sheep became the first mammal to be cloned using fully differentiated somatic adult cells. Cloning has now been successfully used on more than 21 species. The advent of cloning told the scientific community that reprogramming adult mammalian cells was possible, leading to thedevelopment of technology capable reverting adult cells back into stem cells. Generating stem cells from adult cells, induced pluripotent stem (iPS) cells, in addition to thewidespread uses in both research, therapeutics,and regenerative medicine, have reduced the demand for embryonic stem cells, which raises further ethical concerns. On the other hand, advances in gene editing techniques, using CRISPR-Cas9, have opened up new windows to biomedical scientists. Currently, several commercial companies, eitherindependently or as a joint venture, offer services that use this technology for various purposes. To solve future food shortage by the chance to replicate the best animals and therefore enables them to produce a superior quality of products in a shorter time and the potential application of reproductive and therapeutic cloning in the fields of medicine and agriculture in order to test new drugs and treatment strategies are other advantages of this technology. To save endangered species, production of drug-sniffingdogs or those glows in the dark, creation of cattle that cannot develop mad cow disease, production of transgenic cow capable of lactation of human protein in milk are some of the applications of animal cloning. Additionally, the sex, genetic traits and the commercial value of the animals can be known before birth. As part of the upcoming program, De-extinction or bring back the extinct species and to preserve endangered species; setting up the Frozen Zoo that now stores 9,000 vertebrate cells belonging to more than 1,000 different species, are another applications of this technology. In animal cloning, in addition to concern for the reduction of the gene pool, almost 90 per cent of attempts at cloning fail and if it leads to a successful clone, there is still potential for many abnormalities such as organs malformation, deficiencies in the immune system as well as the possible premature ageing. Therefore, animal rights campaigners have condemned this procedure. In 2016, however, a long term study on some cloned sheep found no evidence of a detrimental long-term effect of cloning. Sometimes abnormal cloned fetuses may develop to term, resulting in abnormalities at birth. In large offspring syndrome, as one of the cloning consequences, the offspring may suffer and die from respiratory distress, low-blood sugar, weak immune systems, deformities, and many other problems. The significantly bigger cloned fetus at birth means painful delivery for the mother, which often requiring surgery. Additionally, early pregnancy loss or mid- and late-term spontaneous abortions may be hazardous to surrogates and possibly resulting in retained fetal membranes, metritis (uterine infection), or a mummified fetus. In human, basically, there are two reasons to clone genetic material; the first is for medicine and transplants and the second is for reproduction. Regardless of the global cloning ban in human, from a technical perspective, doing so in humans and other primates is more difficult than other mammals. One of the reasons is missing the proteins which are essential to cell division, known as spindle proteins which during the process of oocyte enucleation are removed from the cytoplasm, and their absence interfere with cell division. While human cloning is now illegal in the world, the application of human stem cells is a very promising field of research. Stem cells can be reprogrammed to become any type of cell needed to repair or replace damaged tissue or cells in the body such as spinal injuries and other cases in regenerative medicine. The possibility to bring back lost child and to choose the traits of the baby Designer Babies , in vitro gametogenesis, and to provide both the sperm and the egg from one parent, one parent children, are other upcoming cloning applications in humans. The idea of creating designer babies was mainly proposed to help humans avoid hereditary diseases using a combination of nuclear transfer and genetic modification. From the point of view of ethical concerns associated with therapeutic cloning and the use of embryonic stem cells, one of the solutions is through the Altered Nuclear Transfer (ANT) technique. In this approach, after silencing the Cdx2 gene of somatic cell nucleus, the cell istransferred to the egg so that it prevents the resultant zygote from developing the potential capabilities of becoming an embryo whilst simultaneously allowing it to produce pluripotent stem cells. Apart from ethical issues regarding human cloning, the risk of mutations, the development of new diseases and in the case of therapeutic cloning the similarities between stem cells and cancer cells and the possibility of accumulation of mutations that may lead to cancer are major concerns. In conclusion, whatever issues reproductive and therapeutic cloning have, combination of this technology with two breakthrough techniques in stem cell biology and gene-editing is the most promising option for future applications in the ields of therapies, biomedical and pharmaceutical researches, livestock breeding and agriculture. In the future, embryo complementation and the possibility of transplantation of animal organ to human, the idea of creating designer babies to prevent the children with severe genetic disordersbeing born, in vitro gametogenesis, personalizing the future of medicine, to produce the animal as a biological incubator are some of the potential benefits and applications of cloning technology. Undoubtedly, the unintended consequences of using this technology and other related technologies should always be taken into consideration