For thousands of years, humankind has manipulated the genomes of organisms through selective breeding. Perhaps, their biggest breakthrough in this field is using biotechnology to control an organism’s genes directly. American biochemist Paul Berg was the leading pioneer behind this task. He combined deoxyribonucleic acid (DNA) of two viruses to create a recombinant DNA (rDNA) in 1972. Today, genetic engineering is applied in the fields of medicine, agriculture, industry, and research.
Recently, a special kind of genetic engineering is taking the world by storm. Genome editing or gene editing involves the insertion, deletion, modification, or replacement of DNA in a living organism’s genome in specifically targeted locations. This special form of editing was pioneered almost thirty years ago.
❖ THE PROCESS OF GENE EDITING
➢ DSB Repair:
DNA Double-Stranded Break (DSB) repair mechanics is one of the basic concepts in gene editing. Non-Homologous End Joining (NHEJ) and Homology Directed Repair (HDR) are two primary DSB repair methods. NHEJ utilizes various enzymes to join DNA ends directly. In contrast, HDR enlists the aid of a homologous structure used as a template to regenerate missing DNA sequences at certain breakpoints.
➢ Engineered Nucleases:
The most crucial part of genome editing is to create a DSB at a precise point inside the genome. To overcome the challenges of performing this task, researchers have identified and bioengineered three ways to create site-specific DSB. The three ways are Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALEN), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs).
➢ Zinc Finger Nucleases (ZFNs):
The ideology behind ZFNs technology is centered on the prime concept of DNA cutting catalytic domain, which is not specific. Therefore, it can later be linked to a particular DNA sequence that recognizes peptides such as zinc fingers. The first step in this road to success is identifying an endonuclease with a separate cleaving site and DNA recognition site.
➢ Transcription Activator-Like Effector Nucleases (TALENs):
The specific DNA binding proteins that feature a collection of 33 or 34 amino acid repeats is known as Transcription activator-like Effector Nucleases (TALENs). The fusion of a nuclease’s DNA cutting domain to TALE domains results in designing the artificial restriction enzymes.
➢ Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs):
The Japanese Osaka University’s team of researchers led by Yoshizumi Ishino discovered this DNA sequence by accident in 1987. Based on this, one of the most impactful discoveries in the history of biology took place 25 years later. In 2012, American biochemist Jennifer Anne Doudna and French researchers Emmanuelle Marie Charpentier published their findings that it is possible to program CRISPR-Cas9 with RNA to edit genomic DNA. This revolutionary discovery means that gene editing has become easier to implement. The impact of the discovery was such that, eight years later, both Jennifer Anne Doudnaand Emmanuelle Marie Charpentier were awarded the Nobel Prize in Chemistry in 2020.
❖ APPLICATION OF GENE EDITING
Researchers have developed a wide array of experimental systems to make use of gene editing efficiently. Gene editing allows the creation of chromosome rearrangement, gene therapy, targeted mutation of genes, labeling endogenous genes, studying the functions of genes with stem cells, etc.
Although they are experimenting mostly on plants and animals, they also use gene editing in the selective therapy of human diseases.
➔ Cancer Research:
The application of gene-editing technology in the engineering of tumor-targeted T cells and hematopoietic stem cells (HSCs) has instituted the concept of gene modification. This has led to beliefs that cancer cells can be modified to make them harmless, thus saving lives. Tango Therapeutics, along with Gilead Sciences, are working together to develop immune-oncology therapies. The former is also attempting to develop medicines that directly target particular tumors.
➔ Cardiovascular Disease (CVD):
One of the leading causes of death in many countries is Cardiovascular Disease (CVD). Many different types of this serious health hazard are often associated with a solitary genetic mutation or a combination of rare mutations that are inherited. While clinical treatments focus on relieving pain and symptoms of the disease, they never treat the mutations. Gene editing has enabled engineers to modify the mutated cells and eradicate the issues once and for all. A biotech company, Verve Therapeutics, is leading efforts to develop medicines for this cause.
➔ Metabolic Diseases:
Genetic factors and the environment are the root causes of metabolic diseases. The disease refers to the pathological condition of the human body’s fat, proteins, carbohydrates, etc., which are disordered metabolically. The advent of gene editing has enabled the technology to be applied in gene therapy and functional gene screening. It also permits the making of metabolic disease models of obesity, hyperlipidemia, and diabetes.
❖ FUTURE OF GENE EDITING
Although many people were skeptical of gene editing initially and furiously criticized it, this behavior exists in only a minority of critics now. The recent revolutionary advancements in biology, biotechnology, and genetic engineering have led the world towards a path of future success.
Perhaps the most solidifying statement in favor of genetic editing is the Nobel Prize in Chemistry won by Jennifer Anne Doudna and Emmanuelle Marie Charpentier in 2020 for their ground-breaking findings of CRISPR-Cas9 Programming in 2012.
Furthermore, many new pieces of research have shown that a new Agricultural Revolution is near the horizon. The fast-growing human population and the changing climate and global warming issues are increasingly difficult to feed the population. As a result, gene editing can help develop genetically modified crops that can withstand the callous changing climatic conditions and reduce the adverse effects of agriculture on Earth. Additionally, it will ensure food security globally and have the nutritional value necessary for humans and animals. Moreover, Latin American researchers are breeding strong variants of fruits and staple crops that are climate resilient and improve digestibility.
On the other hand, researchers at Japanese startup, Sanatech Seeds have developed a genome-edited tomato that can reduce blood pressure. These tomatoes contain high levels of Gamma-AminoButyric Acid (GABA), which helps the cause.
Although gene editing has come a long way over the years, it is still not error-free. The technology still makes errors, which scientists are trying to find out why and if it will cause further issues in human bodies.
Last but not least, gene editing has a long journey ahead of itself to break free from the ethical, social, and technical barriers. Yet, considering the growing concerns about the environmental situation of Earth, gene editing might be our best bet at survival.
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