Draft:Somatic Genetic Engineering

Introduction –

Somatic gene engineering is a field of genetic modification involving the alteration of genes of somatic [non-reproductive] cells in a living organism . Unlike germline engineering (which targets the sperm and egg), somatic engineering will not impact future generations. Somatic engineering focuses on modifying cells within the body that do not contribute to inheritance. This technology is very promising for treating genetic disorders, enhancing therapeutic interventions, and improving tissue regeneration .

History –

Gene therapy dates back to the early 1970’s, when researchers started looking into the potential alteration of genes to treat disease . Herbert Boyer and Stanley Cohen worked together to develop recombinant DNA technologies with the ability to cut and paste DNA from different organisms. They accomplished this by cutting open a plasmid loop in a certain species of bacteria and adding a gene from another bacteria species. Upon further observation, it was found that the bacteria could use this new gene that contributed to its recombinant DNA. Early research looked at germline gene editing, then, due to ethical concerns and technical challenges, it shifted to somatic gene engineering as somatic engineering was far less controversial. In the 1980’s scientists first started experimenting with gene therapy, as they tried to introduce functional genes into somatic cells to correct genetic disorders . The first trials were conducted in the 1990’s when the FDA approved trials for treating SCID (severe combined immunodeficiency) in children . This trial was done on Ashanti DeSilva and involved removing white blood cells and replacing them with modified cells. It was successful in reducing symptoms and allowed her to attend school. This was a major milestone, but initial trials faced many challenges . Today, trials are much safer and more efficient .

Applications –

Somatic gene engineering has many potential applications. Some are: 1. Gene Therapy for Genetic Disorders One of the most promising uses of somatic gene engineering is treatment for genetic disorders (like cystic fibrosis, muscular dystrophy, and sickle cell anemia) . This can be done by the introduction of functional genes, which should compensate for the defective or missing genes. This alleviates some of the symptoms or may even cure the condition . 2. Cancer Treatment Gene engineering has been explored as a treatment method for cancer. This research aims to modify immune cells (like T-cells) to target and destroy cancer cells more effectively. This approach is called gene-modified immunotherapy or CAR-T therapy. It has shown to be effective for blood cancers such as Leukemia or lymphoma . 3. Regenerative Medicine Somatic gene engineering shows significant promise in regenerative medicine, where genes can be edited to promote tissue repair or regeneration . This can be used in the treatment of heart disease, spinal cord injuries, and liver cirrhosis, as well as many other conditions. It works by stimulating growth of healthy cells to repair damaged tissues . 4. Infectious Disease Another potential application is gene editing to eliminate viruses. This option is for infectious diseases and could be used for HIV or hepatitis treatments by utilizing gene editing technologies like CRISPR to eliminate a virus from an infected cell .

Methods of Somatic Gene Engineering –

Somatic gene engineering relies on a technique to deliver and insert new genetic material into a targeted cell. Some tools used for this include viral vectors, non-viral vectors, or CRISPR-Cas9. Viral vectors are modified to be harmless and are used to deliver new genes into a somatic cell . The virus enters a target cell as it typically would, using the shell of the virus to carry the desired gene into the cell. Then, the vector can integrate the new genetic material into the cell's DNA. The genetic material has now been modified to perform the desired function (like to produce a therapeutic protein or to replace a defective gene). Non-Viral Vectors, such as electroporation, lipid nanoparticles, or physical techniques, do not originate from viruses . These methods are safer, but they are less efficient than the viral method. CRISPR-Cas9 is a new technology that allows for precise and targeted editing of the genome. CRISPR is used to cut DNA at a specific location, then enabling the insertion of correct gene . CRISPR has very high accuracy and has recently become a key tool in research.

Challenges –

Somatic gene engineering faces several challenges that can make it unsafe and non-effective. One of these challenges is delivery efficiency. This is a main obstacle as therapeutic genes need to reach the target cell to incorporate into the genome and improve function . The efficiency of gene delivery is a highly intense realm of research because workers are always aiming to improve it . Another challenge is the immune system response. As foreign genes are introduced, it can provoke an immune response which can reduce the effectiveness of the treatment as well as causing harmful side effects . Researchers are looking for ways to minimize the immune reaction, such as the non-viral delivery method. Long-term effects like safety and efficacy are still uncertain. Early results of introducing new genes into species appear promising, but later consequences, like unintended genetic changes, cancer risks, or immune tolerance could be possible . The final major challenge is ethical and regulatory issues. These are centered around safety, consent, and access to treatment. Regulatory bodies are working to set clear guidelines, but this takes time with patient safety and long-term monitoring.

Future Directions –

The future of somatic gene engineering looks promising with many advancements being made in gene editing technologies, delivery systems, and understanding of gene therapy’s applications . Professionals continue to work on expanding its involvement in medicine, using precise methods to treat many diseases . A recent example of this is a sixteen-year-old girl that has been cured of her T-cell leukemia after receiving a therapy created by David Liu. This therapy involves base editing, which allows professionals to change DNA nucleotide bases from a C to a T, T to a C, A to a G, or G to an A. Since many genetic conditions result from an altered sequence of the nucleotide bases, this practice can be applied to many different medical cases. If these methods continue to be successful, relief can be offered to many patients and their families. Ongoing clinical trials also continue to test for safety and efficacy of somatic therapies, with several therapies already approved . There is continued collaboration between researchers, healthcare professionals, and policy makers addressing the challenges as well as searching for the full potential of somatic engineering . However, because there are still many concerns and disagreements involved with current animal studies, many are hesitant to take on the risks of human studies .

Also See –

- Gene therapy

- CRISPR – Ca9

- Gene Editing

- Regenerative Medicine

- Stem Cell Therapy