Independent consultant, UK.
Altern Lab Anim. 2014 May;42(2):137-45. doi: 10.1177/026119291404200206.
The scientific basis and advantages of using recently developed CRISPR/Cas-9 technology for transgenesis have been assessed with respect to other production methods, laboratory animal welfare, and the scientific relevance of transgenic models of human diseases in general. As the new technology is straightforward, causes targeted DNA double strand breaks and can result in homozygous changes in a single step, it is more accurate and more efficient than other production methods and speeds up transgenesis. CRISPR/Cas-9 also obviates the use of embryonic stem cells, and is being used to generate transgenic non-human primates (NHPs). While the use of this method reduces the level of animal wastage resulting from the production of each new strain, any long-term contribution to reduction will be offset by the overall increase in the numbers of transgenic animals likely to result from its widespread usage. Likewise, the contribution to refinement of using a more-precise technique, thereby minimising the occurrence of unwanted genetic effects, will be countered by a probable substantial increase in the production of transgenic strains of increasingly sentient species. For ethical and welfare reasons, we believe that the generation of transgenic NHPs should be allowed only in extremely exceptional circumstances. In addition, we present information, which, on both welfare and scientific grounds, leads us to question the current policy of generating ever-more new transgenic models in light of the general failure of many of them, after over two decades of ubiquitous use, to result in significant advances in the understanding and treatment of many key human diseases. Because this unsatisfactory situation is likely to be due to inherent, as well as possibly avoidable, limitations in the transgenic approach to studying disease, which are briefly reviewed, it is concluded that a thorough reappraisal of the rationale for using genetically-altered animals in fundamental research and by the pharmaceutical industry, and for its support by funding bodies, should be undertaken. In the meantime, the use of CRISPR/Cas-9 to generate new transgenic cells in culture is to be guardedly encouraged.
已针对其他生产方法、实验动物福利以及人类疾病转基因模型的科学相关性，评估了最近开发的 CRISPR/Cas-9 技术在转基因方面的科学依据和优势。由于新技术简单直接，可靶向引起 DNA 双链断裂，并能在单一步骤中导致纯合变化，因此比其他生产方法更准确、更高效，并且加快了转基因的进程。CRISPR/Cas-9 还避免了胚胎干细胞的使用，并且正被用于生成转基因非人类灵长类动物（NHPs）。虽然这种方法减少了因生产每个新品系而导致的动物浪费量，但由于其广泛应用可能导致转基因动物数量的总体增加，任何对减少动物的长期贡献都将被抵消。同样，由于使用更精确的技术减少了不必要的遗传效应的发生，因此通过广泛使用来提高改良水平的贡献也将被日益有感知力的物种的转基因品系的大量生产所抵消。出于伦理和福利原因，我们认为只有在极其特殊的情况下才应允许生成转基因 NHP。此外，我们提供了信息，这些信息从福利和科学的角度出发，使我们对当前的政策产生了质疑，即鉴于许多转基因模型在经过二十多年无处不在的使用后，并没有导致在理解和治疗许多关键人类疾病方面取得重大进展，因此应不断生成新的转基因模型。鉴于对疾病进行研究的转基因方法存在内在的、可能是可以避免的局限性，简要回顾了这些局限性，因此得出结论，应该对在基础研究中以及制药行业中使用遗传修饰动物的合理性进行全面重新评估，并由资助机构提供支持。同时，应谨慎鼓励使用 CRISPR/Cas-9 在培养的细胞中生成新的转基因细胞。
