Avatar Medicine
Avatar medicine uses medical research and development, , detection and diagnosis, and treatment assistance based on individualized samples or data. By using physical or virtual avatars instead of the human body, Avatar medicine is able to decrease the risks, as well as time and distance constraints, that can come with using patients’ actual bodies for tests.
A typical medicine mainly uses patients’ own symptom descriptions and routine examinations to diagnose diseases through clinical data and physician experience. When a disease is diagnosed, the same treatment plans or medication options are often recommended for similar diseases. However, in reality, these treatment effects vary widely based on the patients, even if they have the same disease. In order to break the myth of a “one-size-fits-all medicine”, a new generation of personalized precision medicine has been launched, which focuses more on the biomolecules of the disease (DNA, protein, metabolite). After comparing and analyzing the patient's disease development with the database, it can help doctors more accurately predict and narrow the treatment plan, increasing the medicine's efficiency compared to a typical medicine.
Although genetic testing can use the different genomic information of individuals to provide similar tests, many medical industries are focusing on avatar medicine. At the same time, they are continuing to improve the shortcomings of genetic testing. Currently, the main problem with genetic testing lies in the fact that it tends to ignore disease heterogeneity, and it cannot reflect the dynamic interactions between biomolecules in the human body, such as gene-protein, protein-protein, and protein-metabolite interactions. There has been a long history of using avatar medicine to help diseases such as diabetes, Parkinson's disease, and cancer. In modern times, it is now important to open the door to precision medicine to allow for a future of smarter cancer medicine. This medical revolution will help achieve the goal of helping patients maximize treatment while minimizing side effects.
History - From Precision Medicine to Avatar Medicine
* Back in 1979, scientists were able to use advances in biotechnology to transfect the human insulin gene into the plastids of Escherichia coli. This genetic recombination technology of producing human insulin by using Escherichia coli or yeast became the predominant method for insulin production for type 1 diabetes patients.
* In 2003, advances in DNA sequencing technology helped led to the successful completion of the Human Genome Project. Since then, not only have people unlocked the sequencing of human genes, but subsequent genetic testing has also been applied to precision medicine to find the relationship between specific genetic variants and diseases. Especially after the advent of the method, there has been new advances in the development of biotechnology and medical fields. This includes new technological research innovation, testing reagents and drug development. Additionally, the emersion of a more established complete personal genetic database and additional chemical medicine information have continued to help individuals.
* In January 2015, former US President Barack Obama launched the "Precision Medicine Initiative" in his State of the Union address and was committed to establishing a medical data database of millions of people. The main goal was to understand how a person's genetics, lifestyle and environment can help determine the best method to treat diseases. By collecting information about patient's metabolomics, microbiome and previous health care data, this information can be shared across different providers, researchers and patients. While still ensuring patients’ privacy is protected, this initiative allows for more insight into specific characteristics — such as genetic makeup or genetic profile of an individual's tumor — to continue to help more patients.
* With high-sensitivity gene detection methods, scientists have switched from a general treatment method. By finding the original gene that causes the mutation of normal cells to transform into cancer cells, scientists are able to get a clear target gene for the targeted drugs they use for treatment. These targeted drugs include small molecule drugs and monoclonal antibodies. Unlike chemotherapy drugs, targeted drugs are highly precise and specifically target cancer cells with specific genetic mutations without affecting or harming normal cells. This allows there to be minimal side effects. The most classic example of cancer targeted therapy is non-small cell lung cancer. Specifically, the corresponding inhibitor, EGFR-TKI (Erlotinib, Gefitinib, Afatinib, Osimertinib) is designed for the excessive production of EGFR-TK mutation. Through this technology, survival of patients with advanced lung cancer is greatly improved.
* In 2021, the idea of avatar medicine began to be promoted. Currently, there's still ongoing research to bridge the gaps of interpretation and clinal information for precision medicine, which explains the ambiguous clinical cancer treatment rate. Usually, the treatment effectiveness can only be determined after the patient has received the treatment personally. However, this typically causes the patients to miss the optimal time for treatment, but also increases the chance of their cancer growing due to wrong or ineffective drug use. Therefore, the goal of avatar medicine is not to replace precision medicine, but to reflect the beneficial applications of precision medicine through the help of precision tools. The multimodality and integration of avatar medicine is expected to become a new trend in the treatment of cancer and other diseases in the future.
Entity Avatar
Tumor Organoid
Tumor-derived organoids are 3D cultured in vitro tumor cells isolated from patient tumor tissue. Certain required growth factors are added to establish a state close to the tumor microenvironment in vivo to form a tumor micromodel. Tumor tissue sources include in situ or of patients. Today, successful established tumor organoids include colorectal cancer, prostate cancer, gastric cancer, breast cancer, pancreatic cancer, endometrial cancer and ovarian cancer. Compared with the laboratory cancer cell line culture system, tumor organoids can simulate the morphological structure and functional properties of in vivo tumors and preserve the characteristics of tumor heterogeneity. This provides a big advancement in the field of cancer research and treatment, as it can be used in cases such as anti-cancer drug sensitivity, radiation sensitivity and physical sensitivity tests.
Mouse Avatars
Using current advancement of gene editing technology, researchers have successfully established an immuno-deficient mouse strain to solve the problem of immune rejection of allografts or xenografts. Immune deficient mice refer to mice that contain one or more immune cells (NK cells, T lymphocytes, B lymphocytes, etc.) are ineffective or absent due to congenital genetic mutations or artificial methods. The more common ones are BALB/c nude mice, NOD/SCID, severe immuno-deficiency mice BRGSF and C-NKG mice. The specific method of an immuno-deficiency mouse mode is to xenotransplant a human tumor specimen derived from a patient into mice. The transplantation method can be divided into subcutaneous inoculation or in situ inoculation. When the tumor grows to a certain volume, the tumor is separated and re-inoculated into several immunized mice. The deficient mice are called avatar mice. This allows scientists to conduct different drug tests simultaneously according to individual tumor characteristics after replicating a large number of avatars. Additionally, this allows user to further track the in vitro evaluation of tumor proliferation, invasion and metastasis potential, as well as the exploration of cancer mechanism.
Zebrafish
The genome of zebrafish (Danio rerio) has a high homology of around 70% to 80% with that of humans, so it is often used as an animal model organism for research. Studies also indicate that up to 82% of human disease-inducing proteins are homologous to zebrafish. The zebrafish embryo is transparent, which means it can be used to observe abnormal tumor proliferation, migration, metastasis and other behaviors, and even the real-time monitoring of the whole animal. There are other benefits of using zebrafish as a cancer research model. There only need to be less than 500 transplanted cancer cells for successful vaccination, and within eight days after fertilization (8-day post fertilization, 8dpf), the immune system of zebrafish embryos has not been fully established yet, which means that xenograft rejection did not happen. This allows researchers to xenograft patient-derived cancer cells into zebrafish embryos without prior treatment with artificial immunosuppression. In addition, because zebrafish are small animals, as long as they are treated with drugs for about two days, it is possible to observe whether the tumor is effective or not.
Drosophila
Drosophila melanogaster and human genome sequence homology is as high as 80%, and human and Drosophila share 75% of the same pathogenic genes. Drosophila reproduces rapidly, producing up to 200 offspring in a reproductive cycle of about 12 days, so the Drosophila model can be a better alternative to the higher-cost mouse animal model. It is currently known that the occurrence of cancer is not only regulated by a single gene mutation but is often caused by the simultaneous mutation of multiple genes. Therefore, by regulating related cancer genes' expression in Drosophila, it is possible to model the disease progression and drug resistance of cancers with polygenic mutations and perform high-throughout large-scale drug screening.
Organ on a Chip
is a novel 3D cell culture and drug testing and screening platform that combines bioengineering, 3D printing, microfluidics and other technologies. Through this technology, single organ, organoid and even multi-organ chips have been developed. The biggest advantage of the organ chip is that it can truly reflect the physiological appearance of the human body. The main reason is that it can combine two or more tissues on the same chip, which can precisely control the diversity of the microenvironment in the body and explore the interaction between tissues, allowing for further analysis of physical properties, biochemistry, monitoring metabolic activity and more. At the same time, in terms of personalized avatar medicine, organ chips can create bionic chips belonging to patients, which can simulate physiological functions or disease physiology in the human body, such as tumor microenvironment, provide in vitro pathological mechanism research and predict drug effects. For pharmaceutical companies, it can save money and time in preclinical new drug research and development, observe pharmacokinetics and metabolism, and break through the deviation data that may occur due to different species of animals and humans. This will help the future with new drug research and development processes, while decreasing demand for animal testing.
A typical medicine mainly uses patients’ own symptom descriptions and routine examinations to diagnose diseases through clinical data and physician experience. When a disease is diagnosed, the same treatment plans or medication options are often recommended for similar diseases. However, in reality, these treatment effects vary widely based on the patients, even if they have the same disease. In order to break the myth of a “one-size-fits-all medicine”, a new generation of personalized precision medicine has been launched, which focuses more on the biomolecules of the disease (DNA, protein, metabolite). After comparing and analyzing the patient's disease development with the database, it can help doctors more accurately predict and narrow the treatment plan, increasing the medicine's efficiency compared to a typical medicine.
Although genetic testing can use the different genomic information of individuals to provide similar tests, many medical industries are focusing on avatar medicine. At the same time, they are continuing to improve the shortcomings of genetic testing. Currently, the main problem with genetic testing lies in the fact that it tends to ignore disease heterogeneity, and it cannot reflect the dynamic interactions between biomolecules in the human body, such as gene-protein, protein-protein, and protein-metabolite interactions. There has been a long history of using avatar medicine to help diseases such as diabetes, Parkinson's disease, and cancer. In modern times, it is now important to open the door to precision medicine to allow for a future of smarter cancer medicine. This medical revolution will help achieve the goal of helping patients maximize treatment while minimizing side effects.
History - From Precision Medicine to Avatar Medicine
* Back in 1979, scientists were able to use advances in biotechnology to transfect the human insulin gene into the plastids of Escherichia coli. This genetic recombination technology of producing human insulin by using Escherichia coli or yeast became the predominant method for insulin production for type 1 diabetes patients.
* In 2003, advances in DNA sequencing technology helped led to the successful completion of the Human Genome Project. Since then, not only have people unlocked the sequencing of human genes, but subsequent genetic testing has also been applied to precision medicine to find the relationship between specific genetic variants and diseases. Especially after the advent of the method, there has been new advances in the development of biotechnology and medical fields. This includes new technological research innovation, testing reagents and drug development. Additionally, the emersion of a more established complete personal genetic database and additional chemical medicine information have continued to help individuals.
* In January 2015, former US President Barack Obama launched the "Precision Medicine Initiative" in his State of the Union address and was committed to establishing a medical data database of millions of people. The main goal was to understand how a person's genetics, lifestyle and environment can help determine the best method to treat diseases. By collecting information about patient's metabolomics, microbiome and previous health care data, this information can be shared across different providers, researchers and patients. While still ensuring patients’ privacy is protected, this initiative allows for more insight into specific characteristics — such as genetic makeup or genetic profile of an individual's tumor — to continue to help more patients.
* With high-sensitivity gene detection methods, scientists have switched from a general treatment method. By finding the original gene that causes the mutation of normal cells to transform into cancer cells, scientists are able to get a clear target gene for the targeted drugs they use for treatment. These targeted drugs include small molecule drugs and monoclonal antibodies. Unlike chemotherapy drugs, targeted drugs are highly precise and specifically target cancer cells with specific genetic mutations without affecting or harming normal cells. This allows there to be minimal side effects. The most classic example of cancer targeted therapy is non-small cell lung cancer. Specifically, the corresponding inhibitor, EGFR-TKI (Erlotinib, Gefitinib, Afatinib, Osimertinib) is designed for the excessive production of EGFR-TK mutation. Through this technology, survival of patients with advanced lung cancer is greatly improved.
* In 2021, the idea of avatar medicine began to be promoted. Currently, there's still ongoing research to bridge the gaps of interpretation and clinal information for precision medicine, which explains the ambiguous clinical cancer treatment rate. Usually, the treatment effectiveness can only be determined after the patient has received the treatment personally. However, this typically causes the patients to miss the optimal time for treatment, but also increases the chance of their cancer growing due to wrong or ineffective drug use. Therefore, the goal of avatar medicine is not to replace precision medicine, but to reflect the beneficial applications of precision medicine through the help of precision tools. The multimodality and integration of avatar medicine is expected to become a new trend in the treatment of cancer and other diseases in the future.
Entity Avatar
Tumor Organoid
Tumor-derived organoids are 3D cultured in vitro tumor cells isolated from patient tumor tissue. Certain required growth factors are added to establish a state close to the tumor microenvironment in vivo to form a tumor micromodel. Tumor tissue sources include in situ or of patients. Today, successful established tumor organoids include colorectal cancer, prostate cancer, gastric cancer, breast cancer, pancreatic cancer, endometrial cancer and ovarian cancer. Compared with the laboratory cancer cell line culture system, tumor organoids can simulate the morphological structure and functional properties of in vivo tumors and preserve the characteristics of tumor heterogeneity. This provides a big advancement in the field of cancer research and treatment, as it can be used in cases such as anti-cancer drug sensitivity, radiation sensitivity and physical sensitivity tests.
Mouse Avatars
Using current advancement of gene editing technology, researchers have successfully established an immuno-deficient mouse strain to solve the problem of immune rejection of allografts or xenografts. Immune deficient mice refer to mice that contain one or more immune cells (NK cells, T lymphocytes, B lymphocytes, etc.) are ineffective or absent due to congenital genetic mutations or artificial methods. The more common ones are BALB/c nude mice, NOD/SCID, severe immuno-deficiency mice BRGSF and C-NKG mice. The specific method of an immuno-deficiency mouse mode is to xenotransplant a human tumor specimen derived from a patient into mice. The transplantation method can be divided into subcutaneous inoculation or in situ inoculation. When the tumor grows to a certain volume, the tumor is separated and re-inoculated into several immunized mice. The deficient mice are called avatar mice. This allows scientists to conduct different drug tests simultaneously according to individual tumor characteristics after replicating a large number of avatars. Additionally, this allows user to further track the in vitro evaluation of tumor proliferation, invasion and metastasis potential, as well as the exploration of cancer mechanism.
Zebrafish
The genome of zebrafish (Danio rerio) has a high homology of around 70% to 80% with that of humans, so it is often used as an animal model organism for research. Studies also indicate that up to 82% of human disease-inducing proteins are homologous to zebrafish. The zebrafish embryo is transparent, which means it can be used to observe abnormal tumor proliferation, migration, metastasis and other behaviors, and even the real-time monitoring of the whole animal. There are other benefits of using zebrafish as a cancer research model. There only need to be less than 500 transplanted cancer cells for successful vaccination, and within eight days after fertilization (8-day post fertilization, 8dpf), the immune system of zebrafish embryos has not been fully established yet, which means that xenograft rejection did not happen. This allows researchers to xenograft patient-derived cancer cells into zebrafish embryos without prior treatment with artificial immunosuppression. In addition, because zebrafish are small animals, as long as they are treated with drugs for about two days, it is possible to observe whether the tumor is effective or not.
Drosophila
Drosophila melanogaster and human genome sequence homology is as high as 80%, and human and Drosophila share 75% of the same pathogenic genes. Drosophila reproduces rapidly, producing up to 200 offspring in a reproductive cycle of about 12 days, so the Drosophila model can be a better alternative to the higher-cost mouse animal model. It is currently known that the occurrence of cancer is not only regulated by a single gene mutation but is often caused by the simultaneous mutation of multiple genes. Therefore, by regulating related cancer genes' expression in Drosophila, it is possible to model the disease progression and drug resistance of cancers with polygenic mutations and perform high-throughout large-scale drug screening.
Organ on a Chip
is a novel 3D cell culture and drug testing and screening platform that combines bioengineering, 3D printing, microfluidics and other technologies. Through this technology, single organ, organoid and even multi-organ chips have been developed. The biggest advantage of the organ chip is that it can truly reflect the physiological appearance of the human body. The main reason is that it can combine two or more tissues on the same chip, which can precisely control the diversity of the microenvironment in the body and explore the interaction between tissues, allowing for further analysis of physical properties, biochemistry, monitoring metabolic activity and more. At the same time, in terms of personalized avatar medicine, organ chips can create bionic chips belonging to patients, which can simulate physiological functions or disease physiology in the human body, such as tumor microenvironment, provide in vitro pathological mechanism research and predict drug effects. For pharmaceutical companies, it can save money and time in preclinical new drug research and development, observe pharmacokinetics and metabolism, and break through the deviation data that may occur due to different species of animals and humans. This will help the future with new drug research and development processes, while decreasing demand for animal testing.
Comments