the Evolution of Cell and Gene Therapies: From Science Fiction to Scientific Reality
| 5 min read
Once a realm of speculative fiction, cell and gene therapies (CGT) have now become a cornerstone of modern medicine. Back in the 1970s, TIME magazine captured the public’s inventiveness—and anxiety—with a cover story titled, “The DNA Furor: Tinkering With Life,” which spotlighted the emerging possibilities and risks of genetic engineering, human gene transfer, and the creation of potent microorganisms.
The year 1975 marked a pivotal moment with the Asilomar Conference on Recombinant DNA, where scientists gathered to discuss the potential biohazards and regulation of biotechnology. This groundbreaking conference not only ignited a new era for scientific research but also fostered public dialog on science policy. It was here that researchers laid the groundwork for what would later become the NIH Guidelines, providing a framework for oversight in genetic engineering, gene therapy, and gene editing.
Despite the establishment of these regulatory foundations, the journey of CGT wasn’t without its bumps. The late 1990s and early 2000s saw highly publicized setbacks, such as the French SCID trial, where pediatric subjects developed leukemia, and the tragic death of Jesse Gelsinger. Though, as the turn of the century, significant strides have been made in enhancing the safety of gene transfer technologies.The FDA has issued comprehensive guidance documents for CGT research, while advancements in biotechnology, a focus on translational medicine, and increased investments have all contributed to a surge in CGT clinical trials.
by march 2023, the Journal of Gene Medicine reported entries for 3,900 CGT clinical trials across 46 countries. The majority of these trials focused on cancer (68.3 percent) or inherited monogenic diseases (13.1 percent),with the United States leading the charge by undertaking 2,054 trials (52.7 percent).
By September 2024, the U.S. Food and Drug Administration (FDA) has greenlit 38 cell and gene therapies,a significant leap from the seven approvals in 2023. While this progress is commendable, it still falls short of addressing the vast unmet needs of the 7,000 rare diseases that currently lack treatment options. These therapies hold transformative potential, offering not just treatment but potential cures for conditions that have long eluded medical solutions.
“It would be a shame if all we manage to do is approve another two or three gene therapies a year – that’s a failure,” said Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research (CBER), in a 2023 interview. “Success would be that we start to watch what should be, if not exponential, at least some logarithmic progression toward more and more gene therapies being approved.”
6 Key Approaches in Cell and Gene Therapy:
- Gene-modified cellular therapy
- Genetic vaccines
- Gene transfer
- Oncolytics: reprogramming viruses to kill cancer
- Gene editing
- Gene-modified bacteria or phages
One groundbreaking application of this technology is in treating conditions like lupus, where researchers are leveraging B cell-mediated autoimmunity. A study by UC Davis Health demonstrated remarkable results: a single infusion of CAR-T cells eliminated or reduced lupus symptoms, with no relapses observed in patients after two years of follow-up. This success highlights the versatility of cell and gene therapies beyond oncology.
“CAR-T cell therapy paved the way for success in oncology, and now technologies like gene replacement therapy, gene editing, and RNA editing hold tremendous promise as a treatment or cure in many rare diseases where there is significant unmet need,” said Meagan Vaughn, associate clinical director at Krystal Biotech. Krystal Biotech, a pioneering gene therapy company, is dedicated to developing treatments for genetic and life-threatening rare diseases.Their flagship therapy, Vyjuvek, is the first and only re-doseable gene therapy for dystrophic epidermolysis bullosa, marking a critical milestone in the field.
Revolutionizing Medicine: The Promise of Gene Therapy in Treating rare Diseases
In the ever-evolving world of medical science, gene therapy is emerging as a beacon of hope for patients with limited treatment options. One of the most promising advancements is the growth of re-doseable gene therapies, which use viral vectors to deliver therapeutic genes. ”Right now, our focus is on re-doseable gene therapy using a viral vector to deliver the therapeutic gene.We are working towards this as a treatment for Cystic Fibrosis, for patients who do not have any other treatment options,” explains Vaughn, a key figure in the field.
These therapies are notably transformative for rare diseases, offering a lifeline to those who have felt abandoned by traditional medicine. Take the story of Evelyn Villarreal, born with spinal muscular atrophy (SMA), a devastating condition that typically claims the lives of children before their second birthday. Evelyn’s parents had already lost one daughter to the same disease at just 15 months old, so they wasted no time enrolling her in a clinical trial for an experimental gene therapy when she was only eight weeks old.
The results were nothing short of miraculous.Evelyn became the first baby in the trial to roll over—a milestone that brought tears to her neurologist’s eyes. “Our neurologist just cried,” recalled Evelyn’s mother,Elena,in a conversation with the CDC. ”As Evelyn progressed, she was the first one to walk. it brought so much hope.” Today, Evelyn is a thriving ten-year-old who attends school, enjoys science and art, writes stories, swims, and even flies kites.her story, documented in Science, represents a groundbreaking achievement for SMA1 patients.
Gene and cell therapies (CGT) are making strides across various disease areas, with the FDA granting approvals in oncology (10 approvals), infectious disease vaccines (8 approvals), and rare diseases (11 approvals). As the science behind these therapies advances, the industry is shifting focus from categorizing treatments by disease to organizing them based on technology. This reclassification could pave the way for treating an even broader spectrum of conditions in the future.
The potential of gene therapy is immense, and its impact is only beginning to be realized. By leveraging cutting-edge technologies and innovative approaches,researchers are bringing hope to patients and families who once had none. Stay tuned for part two, where we’ll explore how modern tools like decentralized clinical trials and artificial intelligence are accelerating progress in this transformative field.
