iPSCs
people deem it ethical. 49 The current concerns about future ethicality issues tend to revolve around human cloning and the creation of ‘ human-animal chimeras ’. 50 However, the President's Council on Bioethics called iPSCs ‘ ethically unproblematic and acceptable for use in humans ’. 51
Conclusion
To conclude, the goal was to determine which methods of iPSC generation between cytoplasmic RNA delivery, episomal vectors, polycistronic minicircle DNA nonviral vectors, plasmid-based expression and oocyte reprogramming were the best. They were compared on several key criteria: cost, clinical applications, number of papers published on method, efficiency, effectiveness, ethicality. For an overall comparison, protein delivery is currently the worst of the methods discussed. The low efficiency along with no beneficial traits puts it at a large disadvantage. This is likely due to little research into this method at the time of writing and many of these issues may be resolved with more research. It does have the benefit of having the best safety profile of the methods due to no exogenous genetic information being used. This makes it a prime candidate for clinical use in the future. However, this is still not good enough to be fully accepted as a clinical method yet, particularly due to its limited research, meaning it may be hard to determine the consequences for patients more long term. Oocyte reprogramming is the fifth of the five methods presented due to high cost and limited clinical applications. This cost acts as a huge barrier to the amount of research that can be done on a method as it reduces the appeal of research as one cannot produce as many cell lines for the same amount of money as another method of generation and it prevents less well funded labs or labs in poorer countries from conducting research at all. This limited research is also likely to explain the poor clinical application however cannot be dismissed as a factor. It does have high efficiency and effectiveness however these positives are overshadowed by the negative aspects of the method. The fourth best method of iPSC generation is plasmid-based expression. The low programming efficiency combined with the moderate effectiveness makes it the slowest method to generate a sizable number of iPSCs. The moderate cost also acts as a barrier to it meaning that it is less likely to be a prime candidate for large scale tests and treatments. It does have moderate clinical application and a large amount of research done into the method however the amount of time it takes to generate functional iPSCs is too long to look past this. The third best method is cytoplasmic RNA delivery, this is due to a combination of factors. Mainly the low effectiveness combines with the limited clinical application and the moderate amount of research done. One does have to take into account that less research on a method will typically lead to limited clinical application due to fewer human trials and therefore less information on safety. However, this
49 Lomax, G.P. (2022). Regulatory and policy considerations in iPSC research. Current Topics in iPSCs Technology . 50 Volarevic, V., Markovic, B.S., Gazdic, M., Volarević, A., Jovicic, N.U., Arsenijević, N.N., Armstrong, L., Djonov, V.G., Lako, M., & Stojkovic, M. (2018). Ethical and Safety Issues of Stem Cell-Based Therapy. International Journal of Medical Sciences, 15 , 36 - 45. 51 Lo, B., & Parham, L. (2009). Ethical issues in stem cell research. Endocrine reviews, 30 3 , 204-13 .
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