The effectiveness of gene therapy has been well-documented in treating many conditions. However, as of 2021, only 10,000 people have undergone gene therapy. There are quite a few reasons why this is the case. Gene therapy is still a relatively new and experimental field with potential risks, including unknown long-term effects, complex delivery methods, and high costs. Many scientists have also found the technical challenges insurmountable. It is very difficult to introduce new genes into cells of the body and keep them working. The nature of effectively targeting the correct cells and tissues while ensuring that there is sufficient gene uptake remains a substantial challenge. Zolgensma is $1.79 million per treatment. Casgevy is $2.2 million per treatment. Lenmeldy is $4.25 million per treatment. Despite the high prices, the costs for gene therapy care are substantial and the patient populations are very small.
At the moment, gene therapy is primarily used to treat rare disorders. People become gene therapists because it gives them the opportunity to make a significant difference in their patients’ lives. Many of them are not driven by profits but by personal experiences, such as losing loved ones to disease. Gene therapy has also expanded into new areas such as cardiology. Heart disease is the leading cause of death in the US and in the world. 1 in 5 deaths is because of heart disease, and in the US, 805,000 people have a heart attack each year. In the late 1980s, it was shown that direct intra-arterial gene transfer was possible with endovascular catheter techniques.
The first gene therapy drug approved in the Western world is Glybera, which treats lipoprotein lipase deficiency, a rare condition where patients cannot properly break down the fats in their blood. The very first gene therapy trial on humans was conducted in 1990 to treat a 4-year-old girl with Adenosine deaminase (ADA) deficiency. Now in her 30s, da Silva remains active in the general disease community. Gene therapy has worked with and successfully treated: Immune deficiencies, hereditary blindness, hemophilia, blood disease, fat metabolism disorder, cancer, and Parkinson’s disease.
People who have undergone gene therapy often describe their experience as life-changing, with some noting a sense of liberation from their constant sense of worry normally associated with their conditions. Despite this success, many people continue to have concerns about using a newer, innovative therapy. Gene therapy does come with potential risks, such as allergic reactions, organ damage, and even certain kinds of cancer. People raise ethical concerns that gene therapy can distinguish between “good” and “bad” uses and that gene editing could increase healthcare disparities. However, of course, there are advancements in the technology utilized. The creation of high-fidelity variants of CRISPR technology has created a better tool of Cas9 that modifies your DNA. Currently, gene therapy is only accessible to patients who have severe, life-threatening conditions, and even then one can only use it with clinical trials.
Computational technology offers a promising solution to the challenges currently facing career and aspiring gene therapists. PASTE Technology (Programmable Addition via Site-specific Targeting and Excision) represents a significant advancement for larger DNA insertions. PASTE utilizes a fusion protein, which combines the targeting capabilities of CRISPR with the integration abilities of integrases. Integrases are enzymes that add genetic material to the host’s system. The PASTE system has remarkable versatility and can be used for a wide range of insertion sizes, from 1 to over 100 kilobases. One kilobase pair is equivalent to 1,000 base pairs of nucleotides. AI also has a role to play in technology. AI models can predict and have been used to improve the effectiveness of the CRISPR-Cas model by designing better guide RNAs.
The field of cell and gene therapy is experiencing rapid growth, with job postings in the area increasing by approximately 400% from 2019 to 2023, offering excellent career prospects. The field requires a combination of immense scientific knowledge and problem-solving skills. We expect over 60 gene therapies to be on the market by 2030, as well as a tenfold increase in the market size, reaching $52 billion by 2031. Other new approaches blur the line between gene therapy and drug treatment. Antisense oligonucleotides (ASOs) are drugs made up of small strands of DNA or RNA that target mRNA created by the faulty gene. Their role is to prevent the gene from being translated into a “bad” protein, or sometimes trick the cell’s organelles and mechanisms into making a “good” protein. Gene therapy sees a great and expansive future.
Challenges in Gene Therapy: https://learn.genetics.utah.edu/content/genetherapy/challenges/
Recent Advances in CRISPR-based Genome Editing Technology and Its Applications in Ccardiovascular Research: https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-023-00447-x
Recent Advances in CRISPR-Cas9-based Genome Insertion Technologies: https://pmc.ncbi.nlm.nih.gov/articles/PMC10878794/
Four Success Stories in Gene Therapy: https://www.scientificamerican.com/article/four-success-stories-in-gene-therapy/
Genotoxicity: Damage to DNA and its Consequences: https://pubmed.ncbi.nlm.nih.gov/19157059/
