[Reading Science] Nanorobots and Smart Pills... Disease Snipers Are Coming

The Development of Future Drugs: How Far Have We Come?
Utilizing Advanced ICT and Genetic Engineering
Active Development of Personalized Treatments for Intractable Diseases Like Cancer

Humanity has been using medicine for about 4,200 years. Representative examples include natural drug components such as morphine from opium and cocaine from the coca plant. There are also many traditional Eastern herbal medicines, such as Korean herbal medicine. Since the 1900s, with the development of chemistry, chemotherapeutic agents such as Salvarsan (1907), a specific remedy for syphilis, and penicillin (1927), a broad-spectrum antibiotic, were invented, greatly improving human health. However, the medicine of the future is on a different level. With the advancement of nanotechnology, cutting-edge ICT, and genetic engineering, paths to ultra-precise, personalized, and highly efficient disease treatments are opening. It is not an exaggeration to say that we are dreaming of overcoming incurable diseases such as cancer and dementia and achieving “disease-free longevity.”

A laboratory of a major domestic pharmaceutical company. Stock photo. Not related to the article.

Key Issues of Future Medicines

Efficient use of medicines is the biggest challenge. The concept of personalized medicine to reduce side effects and enhance efficacy is actively being researched. Due to genomic differences, humans may respond differently to the same drug. Genes must be analyzed to predict this and use the most suitable medicine. The difference lies in the base pairs present in an individual's genome (DNA). These differences occur approximately once every 1,000 bases and are frequently found in genes related to cancer, kidney disease, mental disorders, and more. Along with this, new concepts of disease prevention and treatment drugs fused with advanced technology, such as biopharmaceuticals?including protein drugs, nucleic acid drugs, gene and cell therapies?as well as nanomedicine and digital healthcare, are also major topics in future pharmacy.

Biopharmaceuticals, commonly discussed as a concept of future medicine, use proteins and nucleic acids (DNA, RNA) derived from humans or living organisms for therapeutic purposes and include gene therapy and cell therapy. Many protein drugs such as growth hormones, insulin, and interferons have already been commercialized. Initially, naturally occurring proteins were used, but nowadays, most are produced in large quantities as recombinant proteins. Recently, antibody therapeutics, well known during the COVID-19 pandemic response, are also a type of protein drug. Antibodies that bind only to specific antigens such as bacterial toxins, viral antigens, or cancer antigens are used as therapeutics to remove the causative antigens of diseases. They neutralize bacterial toxins or bind to viruses to inhibit their entry into cells. In cancer, they bind to specific antigens on cancer cells and kill them.

Professor Mi-ok Lee of Seoul National University College of Pharmacy said at the “Science Talk Lounge for Public Life” hosted by the Korean Federation of Science and Technology Societies last month, "Most therapeutic antibodies are produced under exclusive rights and sold at high prices, but recently, the biosimilar market, which imitates original drugs whose patents have expired, is growing." She added, "Many companies in Korea are also growing by targeting the global market with excellent products."

Nanorobots and Smart Pills Are Coming

Another “mainstay” of future medicine is nucleic acid drugs, which include DNA drugs such as DNA vaccines, mRNA vaccines and therapeutics, and RNA drugs like siRNA-based treatments. DNA vaccines use microorganisms or proteins from microorganisms. They are injected into the human body in DNA form to induce an immune response, prompting B cells to produce antibodies. They are actively researched as treatments for tuberculosis, hepatitis B, viruses, SARS, AIDS virus, and more. In 2021, India granted emergency approval for the first DNA-based COVID-19 vaccine. mRNA vaccines were developed and first used during the COVID-19 response. They consist of mRNA that can produce viral antigens and nanoparticles that encapsulate and deliver the mRNA. Injected into the body, they stimulate immune cells to produce viral antigens, enhancing the immune response.

Recently, mRNA therapeutics based on this technology have also attracted attention. The mRNA-4157 cancer treatment vaccine developed by Moderna last year reduced the risk of death and recurrence by 44% in phase 2 clinical trials, making headlines. Professor Lee explained, "Personalized therapeutics involve extracting cancer tissue from the patient, analyzing the base sequence of cancer antigen genes, designing and producing an mRNA vaccine corresponding to this, and administering it. This induces antibody production that attacks the cancer tissue. It is an advanced biopharmaceutical using mRNA and the patient’s genetic information, which could mark a milestone in cancer treatment."

Alongside this, RNA interference-based RNA therapeutics are also being researched. This is a type of innate immunity that naturally exists and applies the cellular gene surveillance mechanism to remove abnormal RNA. Interfering RNA is used as a disease treatment drug to suppress specific genes. An injectable drug that suppresses the expression of hereditary variant transthyretin (hATTR) protein, which causes peripheral neuropathy, is already on the market.

Gene therapy is also expected to achieve groundbreaking results. It is a technology that treats diseases by administering normal genes or correcting abnormal genes. Depending on the method of introducing genes into the body, it is divided into virus-based or cell-based gene therapy and gene editing tools. DNA containing therapeutic genetic information is injected into viruses or cells and then administered into the body, where it locates abnormal genes and functions to treat the disease.

The U.S. Food and Drug Administration (FDA) has already approved the cell-based gene therapy “Kymriah,” and Zolgensma, a one-time treatment for spinal muscular atrophy (SMA), is already on the market. The CRISPR/Cas9 gene editing tool, which has gene editing capabilities, also offers hope for treating intractable diseases. The gene scissors Cas9 enzyme is administered together with guide RNA. This enables insertion, deletion, amplification, or mutation of specific genetic information in genes, allowing disease cure.

Stem cell therapies have also been researched and developed for a long time and continue to advance. Embryonic stem cells and adult stem cells can be differentiated into specific cells and transplanted into patients to achieve therapeutic effects. However, embryonic stem cells still face ethical controversies. Recently, the “induced pluripotent stem cell method,” which reprograms stem cells obtained from adults into induced pluripotent stem cells for use, is being actively researched.

There are also smart pills, which are bio-convergent intelligent pharmaceuticals. Smart pills accurately locate the desired disease site and continuously deliver the appropriate drug concentration for effective treatment. Drug delivery systems using nanorobots and biosensors are also being developed. Nanorobots injected into the human body automatically release drugs while sensing the internal environment. Representative examples include insulin-supplying robot capsules and bacterial robots. Central nervous system treatment robots that deliver drugs to the brain and spinal cord using magnetic fields are also under development. Digital therapeutics, which assist in disease prevention, drug administration, and management according to physician prescriptions, and digital healthcare technologies combining healthcare and ICT?such as home care systems capable of remote diagnosis, diagnostic sensors, and drug administration?may be commercialized within 10 to 20 years.

A case of nanorobots that can remove tumors without surgery. Image courtesy of the Ministry of Science and ICT.

Professor Lee emphasized, "In the future, with the development of drug delivery technologies, many biopharmaceuticals will be developed as oral drugs, inhalers, or patches, so patients will not have to endure injections they dislike." She added, "Although biopharmaceuticals may have less toxicity and fewer side effects than chemical drugs, they must be designed and produced to minimize immune responses and toxicity, and thorough clinical trials are essential." She continued, "If innovative therapeutic drugs continue to emerge, it is possible that cancer will eventually be overcome."