The following is a framework for experimental design to enhance human immunity to diseases through gene modification so that they are less susceptible to infection. However, it should be emphasized that such experiments involving human gene editing face many strict restrictions and challenges at the ethical, legal and technical levels. Currently, extremely cautious and strict regulatory procedures must be followed worldwide: ### Experimental background Many diseases seriously threaten human health, such as certain infectious diseases (such as influenza, COVID-19, etc.), genetic diseases, etc. Through gene editing technology, it is possible to find ways to enhance the expression or function of immunity-related genes, thereby improving the body's resistance to disease. ### Experimental objectives Verify whether specific gene modifications can significantly enhance human immunity to target diseases and reduce the risk of infection and the severity of the disease. ### Experimental subjects 1. **Recruitment criteria** - Aged between [specific age range], in good health, with no history of major chronic diseases and infectious diseases. - Sign a detailed informed consent form to fully understand the purpose, process, risks and possible consequences of the experiment. 2. **Grouping** - The recruited experimental subjects are randomly divided into an experimental group and a control group. The experimental group undergoes gene modification, while the control group does not undergo gene modification. The two groups are as balanced as possible in terms of age, gender, health status, etc. ### Experimental methods 1. **Gene editing technology selection** - According to the target gene of the study, select the appropriate gene editing technology, such as CRISPR/Cas9 system. 2. **Gene editing operation** - For the experimental group: - Introduce the designed gene editing elements into the target cells (such as hematopoietic stem cells or immune cell precursors) through a suitable vector (such as a viral vector). - Perform gene editing operations in vitro to ensure editing efficiency and accuracy, and detect the expression or functional changes of the target gene in the edited cells. - Infuse the edited cells back into the experimental group individuals to monitor the survival, differentiation and effects of the cells on the immune system in vivo. 3. **Disease exposure and monitoring** - Expose the target disease pathogens to the individuals in the experimental and control groups. The exposure method depends on the type of disease, such as vaccination with live attenuated vaccines, contact with pathogen cultures, etc. - Closely monitor the infection of individuals, including the time of onset and severity of infection symptoms, and determine whether they are infected and the changes in pathogen load after infection through laboratory tests (such as nucleic acid testing, antibody testing, etc.). - Record the changes in various physiological indicators of individuals during the infection period, such as body temperature, blood routine, inflammatory factor levels, etc. ### Experimental evaluation indicators 1. **Immune indicators** - Detect changes in immune system-related indicators of individuals in the experimental group and the control group before and after the experiment, such as lymphocyte subset ratios, immunoglobulin levels, cytokine secretion, etc. 2. **Infection indicators** - Compare the infection incidence of individuals in the two groups, and record the type of infected disease, symptom duration, etc. - For infected individuals, evaluate the disease severity score, such as a comprehensive score based on clinical symptoms, imaging examination results, etc. 3. **Gene expression and functional evaluation** - During the experiment, samples from individuals in the experimental group are collected regularly to detect the expression level of the edited gene and its effect on downstream immune-related genes and signaling pathways. - Through functional experiments, such as in vitro cell experiments, verify whether the edited immune cells have enhanced killing ability and antiviral activity against pathogens. ### Experimental schedule 1. **Preparation phase ([X] weeks)** - Complete experimental design, ethical approval, etc. - Recruit experimental subjects and conduct comprehensive physical examinations and baseline tests. - Prepare gene editing reagents, vectors, detection equipment, etc. required for the experiment. 2. **Gene editing and cell reinfusion phase ([X] weeks)** - Gene editing is performed on the experimental group individuals and the edited cells are cultured and tested in vitro. - The edited cells are reinfused into the experimental group individuals and short-term observation and monitoring is performed. 3. **Disease exposure and monitoring phase ([X] months to [X] years)** - The two groups of individuals are exposed to disease pathogens according to the predetermined plan. - Continuously monitor the infection status of individuals, changes in immune indicators, etc., and collect samples for testing and analysis regularly. 4. **Experimental summary phase ([X] weeks)** - Collect all experimental data and conduct statistical analysis. - Write an experimental report, evaluate the experimental results, and draw conclusions. ### Ethical considerations 1. Strictly follow international and domestic ethical guidelines and laws and regulations on human gene editing to ensure the scientificity, safety, and ethics of the experiment. 2. Fully explain the experimental risks to the experimental subjects and protect their right to know, right to choose independently, and right to privacy. 3. Establish an independent ethics review committee to supervise and review the entire experimental process and promptly identify and resolve possible ethical issues. The above experimental design is only a conceptual framework. The actual implementation of such experiments requires extremely rigorous scientific demonstration, sufficient safety assessment and strict approval from multiple aspects to ensure the safety of the experiment.