Using gene editing technology to adapt humans to high-radiation environments is a very challenging idea involving many complex issues and ethical considerations. It is still in a very preliminary exploration stage and is still very far from practical application. It mainly faces the following difficulties: ### Technical level 1. **Identify key genes** - **In-depth study of radiation damage mechanism**: - First of all, we must have a comprehensive and in-depth understanding of the detailed molecular mechanism of radiation damage to human cells and tissues. Radiation can cause multiple effects such as DNA double-strand breaks, base damage, oxidative stress, and then cause a series of adverse consequences such as cell apoptosis, gene mutation, and chromosome aberration. It is necessary to accurately determine which genes play a key role in radiation protection and damage repair through a large number of cell experiments and animal model studies. - For example, studies have found that some genes involved in the DNA damage repair pathway, such as BRCA1, BRCA2, etc., are crucial in maintaining genome stability. When these genes function normally, they can efficiently repair DNA double-strand breaks caused by radiation, reducing the risk of cells becoming cancerous or dying due to inability to repair damage. - **Genome-wide association study (GWAS)**: - Conduct large-scale genome-wide association studies of the population to compare the genetic differences between people who have been exposed to a long-term low-dose radiation environment and the normal population. Through whole-genome sequencing and phenotypic analysis of a large number of individuals, find gene loci associated with radiation tolerance. - For example, it may be found that single nucleotide polymorphisms (SNPs) of certain genes are associated with differences in individual responses to radiation. Some specific SNPs may affect the expression level of genes or protein functions, thereby affecting the cell's ability to repair radiation damage or antioxidant defense mechanisms. 2. **Gene editing method selection** - **CRISPR/Cas9 system**: - CRISPR/Cas9 is one of the most widely used gene editing technologies. To use it to edit genes related to radiation adaptation, it is necessary to design highly specific guide RNA (gRNA) so that it can accurately target the target gene. - For example, for the key genes for radiation protection identified, the designed gRNA should be able to guide the Cas9 protein to accurately cut the specific location of the gene to achieve gene knockout, gene editing or regulation of gene expression. However, in actual operation, the off-target effect of gRNA is an important issue that needs to be addressed, which may lead to accidental editing of non-target genes and cause unknown biological consequences. - **Other emerging technologies**: - In addition to CRISPR/Cas9, some emerging gene editing technologies are also developing, such as base editors and prime editors. Base editors can directly replace specific bases in DNA without generating double-strand breaks, which may be more conducive to precise gene editing in some cases and reduce the impact on genome stability. - Prime editing technology can achieve more complex gene editing operations, such as replacing, inserting or deleting multiple bases at the same time. These technologies may provide more options and possibilities for optimizing the functions of genes related to radiation adaptation. 3. **Evaluation of gene editing effects** - **Evaluation at the cellular level**: - Gene-edited cells are exposed to different doses of radiation to detect indicators such as cell survival, DNA damage repair efficiency, cell cycle regulation, and antioxidant capacity. - For example, evaluate the proliferation ability of cells after radiation through cloning experiments to observe whether gene editing increases the cloning rate of cells; use comet assay to detect the degree of DNA damage, compare the DNA migration distance of gene-edited cells and unedited cells after radiation, and judge the effect of gene editing on DNA damage repair. - **Animal model evaluation**: - Construct a gene-edited animal model, such as a mouse model. Expose gene-edited mice to whole-body or local radiation to observe changes in their physiological state after radiation, including changes in body weight, recovery of hematopoietic function, degree of tissue and organ damage, etc. - For example, detect changes in the number of white blood cells, red blood cells and platelets in the peripheral blood of mice to evaluate the effect of gene editing on the recovery of the hematopoietic system after radiation; observe the pathological damage of organs such as the liver, lungs, and intestines after radiation through histopathological examination to determine whether gene editing reduces radiation damage to organs. - **Long-term health impact assessment**: - Conduct long-term observations on animals that have been gene-edited and adapted to radiation to monitor their growth and development, reproductive ability, tumor occurrence, etc. Because gene editing may bring some potential long-term effects, such as new gene mutations or chromosomal abnormalities in the long-term proliferation of gene-edited cells, leading to an increased risk of tumors. - For example, tracking the growth of gene-edited mice from infancy to adulthood to observe whether their body shape, behavior, etc. are normal; conducting breeding experiments on adult mice to evaluate whether gene editing has adverse effects on the development and health of their offspring; regularly screening mice for tumors to detect whether tumors occur and the incidence and type of tumors. ### Ethics and