さらに、RNA編集技術を用いた治療法も開発されています。ADAR（Adenosine Deaminase Acting on RNA）を利用して、mRNAの特定の塩基を化学修飾し、タンパク質の機能を調整するアプローチが研究されています。この技術は、従来のCRISPR-Cas9とは異なり、DNA配列を改変せずに遺伝子機能を調整できるため、安全性が高いとされています。
Genetic testing and gene therapy are attracting attention as innovations in modern medicine. These technologies contribute to the early detection of diseases and the realization of personalized medicine, bringing new hope to many patients. However, at the same time, there are technical and ethical challenges that require careful handling.
The current status and potential of genetic testing
Genetic testing is a technology that analyzes an individual’s genetic information to assess the risk of disease and predict drug responses. In recent years, advances in next-generation sequencing technology have made it possible to perform whole-genome analysis quickly and at low cost, and this is expected to serve as the foundation for personalized medicine.
Genetic testing can assess the risk of multifactorial diseases such as cancer, cardiovascular disease, diabetes, etc. For example, mutations in the BRCA1/2 genes are known to increase the risk of breast and ovarian cancer, and people with these mutations may be recommended regular screening and preventive surgery.
2. Prediction of drug response
It is clear that the effects and side effects of drugs vary depending on an individual’s genetic background. For example, polymorphisms in the CYP2C19 gene affect the metabolism of the antiplatelet drug clopidogrel, and the drug’s efficacy may be reduced in patients with certain genotypes. Based on this information, it is possible to select appropriate drugs and adjust dosages.
3. Diagnosis of genetic diseases
Genetic testing is also essential for diagnosing genetic diseases. In single-gene diseases such as muscular dystrophy and cystic fibrosis, identifying the causative gene mutation allows for accurate diagnosis and appropriate management.
Gene therapy is an approach that aims to provide a fundamental cure by correcting, replacing, or introducing the genes that cause the disease. In recent years, many clinical trials have been conducted, and several products have been put into practical use.
1. Successful examples of gene therapy
Zolgensma, a gene therapy for spinal muscular atrophy (SMA), has been shown to improve the motor function of patients by compensating for the missing SMN1 gene. Gene therapy for hemophilia B is also underway, and the introduction of the FIX gene is expected to result in sustained production of clotting factors.
2. Advances in vector development
Adeno-associated viruses (AAV) and lentiviruses are widely used as vectors for introducing genes into cells. AAV has low pathogenicity and is capable of long-term gene expression, making it superior in both safety and efficacy.
3. Challenges and Prospects
On the other hand, gene therapy still faces several challenges. For example, there is a lack of mass production technology and facilities for vectors, and solving these issues is an urgent task. In addition, ensuring safety, including the durability of therapeutic effects and control of immune responses, is also an important theme.
In Japan, too, efforts are underway to put gene therapy into practical use. For example, the Japan Agency for Medical Research and Development (AMED), a national research and development corporation, is promoting regeneration, cell medicine, and gene therapy projects, and is supporting research and development using iPS cells and genetically modified cells.
In addition, the Next Generation Biopharmaceutical Manufacturing Technology Research Association (MAB) is working on the development of mass production and analysis technologies for gene therapy vectors, which are expected to become a strength of Japan in the future.
As genetic testing and gene therapy become more widespread, ethical and social issues are also emerging. For example, there is a need for discussion on the protection of privacy regarding the handling of genetic information and the scope of application of gene therapy. In addition, careful consideration is required regarding the impact of the use of gene modification technology on social diversity.
The latest technology and applications of gene therapy
Gene therapy has made great strides thanks to recent technological innovations. In particular, it is expected to be applied to a wider range of diseases by combining gene editing technology and cell therapy.
1. CRISPR-Cas9 and next-generation gene editing
CRISPR-Cas9 technology is an innovative technology that can precisely edit targeted genes. This technology makes it possible to correct disease-causing genetic mutations, bringing the possibility of treating various genetic diseases into view.
For example, in the case of beta-thalassemia and sickle cell disease (SCD), a treatment has been developed in which hematopoietic stem cells are genetically modified using CRISPR technology and then transplanted into the patient. This method is already undergoing clinical trials and is expected to be highly effective.
Research is also underway to use CRISPR to correct the gene for Duchenne muscular dystrophy (DMD), a type of muscular dystrophy. An approach is being developed to suppress the production of mutant proteins and slow the progression of the disease by removing specific exons.
RNA-based therapy has been attracting attention as a new approach to gene therapy. In particular, the development of mRNA vaccine technology is expanding the possibilities of RNA-based therapy.
For example, antisense oligonucleotide (ASO) therapy is a technology that controls the expression of disease-causing proteins by suppressing the translation of specific mRNA. The drug “Spinraza” has already been approved for the treatment of spinal muscular atrophy (SMA) and is being used in clinical trials.
In addition, treatments using RNA editing technology are also being developed. Research is being conducted on an approach that uses ADAR (Adenosine Deaminase Acting on RNA) to chemically modify specific bases in mRNA to adjust protein function. Unlike conventional CRISPR-Cas9, this technology is considered to be highly safe because it can adjust gene function without modifying the DNA sequence.
In the field of cancer treatment, new therapies that combine gene therapy and immunotherapy are being developed. In particular, CAR-T cell therapy is attracting attention as a treatment that uses gene modification technology to strengthen T cells and target cancer cells.
CAR-T therapy is a technology in which T cells are collected from the patient, genetically modified to recognize antigens specific to cancer cells, and then returned to the body to attack cancer cells efficiently. Currently, CAR-T therapy targeting CD19 is used to treat leukemia and lymphoma, and has been reported to have a high response rate.
Additionally, new immune cell therapies, such as TCR-T cell therapy and gene modification therapy using NK cells, are also being developed.
The future of genetic testing and personalized medicine
Advances in genetic testing are accelerating the realization of personalized medicine (precision medicine). It is now possible to plan treatment strategies based on individual genetic information, enabling the provision of more precise medical care.
1. Use of Polygenic Risk Scores (PRS)
Polygenic risk scores (PRS) are a method for quantifying disease risk by comprehensively evaluating multiple gene mutations, allowing for more accurate assessment of the risk of multifactorial diseases that cannot be explained by single gene mutations.
For example, PRS is used to assess the risk of cardiovascular disease, type 2 diabetes, Alzheimer’s disease, and other conditions, and is useful for early intervention and lifestyle improvements.
Genetic testing is also used to optimize lifestyle habits. For example, by analyzing genes involved in metabolism, it is possible to design optimal diet and exercise programs for individuals.
FTO gene : Involved in obesity risk and susceptibility to the effects of high-calorie diets.
PPARG gene : Affects insulin sensitivity and is involved in carbohydrate metabolism.
CLOCK gene : Associated with circadian rhythms and determines appropriate sleep and exercise timing.
Genetic testing is also used to assess the risk of mental illness. For example, genes known to be involved in depression and anxiety disorders include **5-HTTLPR (serotonin transporter gene) and BDNF (brain-derived neurotrophic factor)**.
People with the truncated (S) form of 5-HTTLPR may be more sensitive to stress and at increased risk of depression.
The Val66Met polymorphism in BDNF may reduce neuroplasticity and affect the brain’s ability to adapt to stress.
Harnessing this genetic information will enable preventive interventions and the design of personalized treatment strategies.
As genetic testing and gene therapy become more widespread, their societal impact is also growing, raising many issues for discussion, including ethical issues, privacy protection, and commercial use of data.
In particular, careful consideration is required regarding discrimination due to the misuse of genetic information, and the handling of genetic risks in insurance and employment. To address these issues, countries are working to establish laws regarding the protection of genetic information.
Developments in genetic technology have the potential to dramatically transform the future of medicine, but it is essential that they are approached carefully and within an appropriate ethical framework.
Technological innovation and expanding applications of gene therapy
New technologies are still being developed for gene therapy, and the scope of its application is expanding. In particular, by combining it with next-generation gene editing technology and cell therapy, it is expected to be applied to diseases that were difficult to treat with conventional treatments.
1. Epigenetics and gene therapy
Epigenetics refers to the mechanism by which gene expression is controlled without changing the base sequence of DNA. Advances in research in this field have led to the emergence of new gene therapy methods that target epigenetic modifications.
For example, attempts are being made to treat cancer and neurodegenerative diseases by regulating histone modifications and DNA methylation. In particular, development of therapeutic agents targeting **DNA methyltransferases (DNMTs) and **histone deacetylases (HDACs)** is underway.
“CRISPR epigenetics,” an application of CRISPR technology, is also attracting attention. Unlike the usual CRISPR-Cas9, this is a technology that controls the expression of specific genes without cutting DNA. This approach makes it possible to suppress the progression of diseases without directly correcting genetic mutations.
For gene therapy to be successful, it is essential to have technology that can efficiently deliver genes to the target cells. Traditionally, viral vectors have been used primarily, but new delivery systems are being developed.
a. Nanoparticle-based gene delivery
Non-viral vectors using liposomes and polymers have been developed as a method to deliver genes into cells without using viruses . In particular, lipid nanoparticles (LNPs), which are used in mRNA vaccines, are also being applied in the field of gene therapy.
This technology, when combined with RNA-based therapeutics, may be useful for the treatment of various diseases, for example, gene delivery using LNPs is being explored for the treatment of liver disease and inherited blood disorders.
In recent years, progress has been made in the development of “cell-directed vectors” that deliver genes only to specific cells or tissues. This reduces the risk of genes being taken up by cells other than the target, making it possible to reduce side effects.
For example, in the treatment of brain diseases, a vector that can pass through the blood-brain barrier (BBB) is required. In recent research, AAV vectors that can pass through the BBB by adding specific peptides have been developed and are being applied to gene therapy for Alzheimer’s disease and Parkinson’s disease.
Immunogene therapy, which treats diseases by activating the immune system, is also progressing. In the field of cancer immunotherapy, genetically modified T cells (CAR-T therapy) have already been put to practical use, but TCR-T therapy and CAR-NK cell therapy are attracting attention as new approaches.
a. TCR-T cell therapy
CAR-T therapy is effective against blood cancers such as B-cell lymphoma, but is considered difficult to apply to solid cancers. In contrast, TCR-T therapy may be applicable to the treatment of solid cancers by introducing T cell receptors (TCRs) that can recognize antigens presented by cancer cells.
Clinical trials of TCR-T therapy are currently underway for melanoma and lung cancer.
Issues with CAR-T therapy include side effects such as cytokine release syndrome (CRS) and neurotoxicity. In contrast, CAR-NK cell therapy, which uses natural killer (NK) cells , is expected to be a highly safe and versatile treatment.
CAR-NK therapy has the potential to be applied not only to blood cancers but also to solid tumors , and many companies and research institutions are currently working on its development.
As the accuracy of genetic testing improves, it is being applied not only to disease diagnosis but also to treatment monitoring. In particular, by combining it with biomarker analysis, more detailed personalized medicine is becoming possible.
1. Liquid biopsy and genetic testing
Liquid biopsy is a technique to detect DNA (ctDNA) and exosomes derived from cancer cells in bodily fluids such as blood and urine. Combining this technique with genetic testing makes it possible to non-invasively detect cancer early and monitor the effectiveness of treatment.
For example, by detecting EGFR gene mutations in lung cancer patients, the suitability of tyrosine kinase inhibitors (TKIs) can be determined and treatment optimized.
Advances are also being made in ” multi-omics analysis ,” which integrates multiple data sets, such as not only genomic (DNA) information but also transcriptome (RNA), proteome (proteins), and metabolome (metabolic products) .
This approach may lead to a deeper understanding of the mechanisms of disease onset and the discovery of new therapeutic targets. For example, it has become clear that in addition to genetic mutations, inflammation and metabolic abnormalities in the brain are involved in Alzheimer’s disease.
It is expected that the combination of genetic testing and biomarker analysis will further advance disease prevention and early diagnosis, enabling more personalized treatment.
Genetic testing is being used in a variety of fields, not just medicine. Advances in technology have expanded the scope of application beyond traditional disease risk assessment and drug response prediction to nutrition, exercise, sleep, and even anti-aging.
1. Development of Nutrigenomics
“Nutrigenomics,” which studies the relationship between nutrition and genes, is a field that proposes nutritional management according to an individual’s genetic characteristics. For example, the following genes are known to affect nutritional metabolism:
The LCT gene : determining risk of lactose intolerance
FTO gene : Influences risk of obesity
PPARG gene : Regulating carbohydrate and lipid metabolism
By utilizing genetic testing, it is possible to design a meal plan that suits an individual’s metabolism and prevent obesity and lifestyle-related diseases. For example, people with a mutation in the FTO gene can reduce their risk of obesity by avoiding high-fat foods.
In addition, because the presence of a mutation in the MTHFR gene reduces the ability to metabolize folic acid, women may be advised to take folic acid supplements before becoming pregnant. Knowing this information in advance will enable more effective nutritional management.
2. The relationship between genes and athletic ability
Sports genetics (exercise genomics) is also attracting attention as a new application field of genetic testing. By analyzing genes related to athletic ability, it is possible to select the most suitable training method for each individual’s physical constitution.
ACTN3 gene : Involved in the development of fast-twitch muscle fibers and determines whether one is suited to sprinting or endurance running
ACE gene : Affects muscle blood flow and endurance
PPARGC1A gene : Involved in mitochondrial function and optimizes energy metabolism
People with the RR type (fully functional) of the ACTN3 gene are suited to short-distance running and power sports that utilize explosive power, while people with the XX type (low-functioning) are suited to sports that require endurance.
It has also been suggested that low-intensity aerobic exercise is more effective than high-intensity interval training (HIIT) in people with certain variants of the PPARGC1A gene. By utilizing such information, we can create a training program that is optimized for individual characteristics.
It has been shown that mutations in the CLOCK gene can disrupt the rhythm of one’s internal clock and make one more susceptible to insomnia and jet lag.
Research has also shown that polymorphisms in the PER3 gene determine whether you are a morning type (long sleeper) or a night type (short sleeper). People with certain PER3 mutations tend to wake up earlier in the morning and feel very sleepy at night.
By utilizing this information, it will be possible to implement measures to improve sleep that are tailored to each individual’s genetic characteristics. For example, people who tend to be night owls can adjust their biological clock by getting into the habit of getting some morning sunlight.
It has become clear that genes are also involved in the speed of aging and longevity. Research into genes related to longevity is progressing, and the following genes have attracted particular attention:
FOXO3 gene : Improving cellular stress resistance and contributing to longevity
SIRT1 gene : Maintaining DNA repair and mitochondrial health
TERT gene : Maintains telomere length and inhibits cellular senescence
It has been reported that people with certain variants of the FOXO3 gene have greater resistance to oxidative stress and a lower risk of developing cardiovascular disease and cancer.
The SIRT1 gene is known to be activated by resveratrol (a polyphenol found in red wine and grapes), and research related to anti-aging is being conducted.
Advances in genetic testing and gene therapy are dramatically changing our lives. We are entering an era in which genetic information can be used not only in conventional medicine, but also in nutrition, exercise, sleep, and aging management.
However, the handling of genetic information requires careful consideration, and it is important to establish regulations to address ethical issues, protect privacy, and prevent the misuse of genetic information.
Genetic testing and gene therapy are making a significant contribution to the prevention of disease and the development of personalized medicine. Applications are expanding beyond disease risk assessment and drug response prediction to the fields of nutrition, exercise, sleep, and anti-aging. While technological innovation continues to advance, ethical issues and the importance of data protection are also increasing, and safe and effective use is required.
