Overcoming High-profile Gene Therapy Failures

Overcoming High-profile Gene Therapy Failures- Gene therapy has been around for decades. While some experiments have resulted in deadly or serious side effects, researchers have persevered in their pursuit of genetic cures. The promise of a gene-based drug makes gene therapy a compelling case. But there are still plenty of lingering questions about the technology. Here’s what you need to know. We’ll touch on CRISPR technology, Editas Medicine, and Jesse’s death.

Table of Contents

Overcoming High-profile Gene Therapy Failures
Overcoming High-profile Gene Therapy Failures

History of Gene Therapy

Editoras Medicine is a biotech company that is using CRISPR and RNA chemistry to develop gene therapies to treat a wide range of genetic diseases, including sickle cell anemia and childhood blindness.

CEO Gilmore O’Neill has come from Biogen and Sarepta Therapeutics and brings a history of driving blockbuster drugs through clinical trials.

In the 1990s, gene therapy was seen as a major breakthrough, but its promise was short-lived. The discovery of the CRISPR-Cas9 gene-editing mechanism by a young researcher, Jennifer Doudna, cast doubt on the efficacy of gene therapy, and the company suffered high-profile setbacks.

The US FDA suspended all gene therapy programs at the university, and launched investigations into 69 other gene-therapy trials. The resulting controversy cast a spotlight on the safety of viral vectors, and the pace at which gene therapy was developed was seen as too rapid.

Despite the setbacks, gene therapy has recovered. In 2003, China approved Gendicine, a gene therapy for head and neck cancer. In 2011, Russia approved Neovasculgen, which treats peripheral artery disease.

And in 2012, the European Commission approved Glybera, a drug made by uniQure. But Glybera, which targets the faulty enzyme lipoprotein lipase, was not a success. It cost EUR1M, and it was only used for one patient.

Despite the high-profile setbacks, Editas Medicine has been making progress in its clinical trials. In March 2020, the first patient was treated with a low-dose of CRISPR gene editing technology.

By November 2020, the entire low-dose cohort had been treated, and the medium-dose cohort is expected to begin.

Wilson’s Vectors

Wilson’s vectors for gene therapy have been used to treat a range of diseases, including sickle cell anemia, rheumatoid arthritis, and ALS.

The concept of gene therapy is simple: genetic diseases result from faulty genes, so giving someone an extra copy of a disease-causing gene is a quick and effective cure.

Wilson’s vectors used therapeutic genes stuffed inside hollowed-out adenoviruses, which are naturally adept at infiltrating cells and propagating their own genes.

This innovative approach had been seen by many scientists as a less controversial alternative to more extreme treatments for a number of diseases, and a great leap forward for gene therapy.

Wilson’s team didn’t consider the innate immune system when designing the viral vectors. The company held the patent rights to the new viruses and didn’t want other groups to get the technology without his permission. In addition, they feared that sloppy experiments would endanger patients.

Wilson’s lab is connected to biotech companies. There are few academics who have turned their biomedical labs into start-up incubators, but his team’s scale is unique. They rely on more experienced scientists to gather data, which they then share with biotech partners.

Amicus Therapeutics signs an agreement with Wilson’s lab for $10 million a year for five years to develop the next generation of AAVs. The lab recently moved into a commercial building down the street. The company will hire 200 people across three floors of the building.

CRISPR technology

While CRISPR technology in gene therapy has experienced high-profile failures, promising results have been reported in recent clinical trials.

The technology works by editing specific cells and tissues without affecting sperm, eggs, or other reproductive tissues. If the technology is successful, it could ultimately help cure blood disorders like sickle cell disease.

But the delivery of these therapies remains a key challenge. Unlike gene therapies delivered through traditional methods, CRISPR technology is a much more precise means of editing the genome of the target cells. While off-target effects are still possible, they have not yet been reported in early clinical trials.


The CRISPR technology is designed to cut the target gene by generating a double-strand break in the DNA. This initiates two endogenous DNA repair mechanisms: non-homologous end joining (NHEN) and homology-directed repair (HDR).

CRISPR technology has been used to edit cancer cells. In particular, CRISPR edits the PD-1 gene to prevent T cells from producing functional PD-1 receptors. This process is called checkpoint inhibition and often works in conjunction with CAR-T engineering.

Despite the high-profile failures, the technology continues to see promising results. While the field has seen some high-profile successes, its side effects remain a concern. To prevent these side effects, researchers must balance progress with caution.

Jesse’s Death

A recent case at the University of Pennsylvania highlights the risks of gene therapy, with Jesse Gelsinger dying from the treatment. The boy was diagnosed with a severe genetic disorder, a disease that can cause a coma or even death.

After an experimental therapy, the University of Pennsylvania instituted the gene therapy in the boy, who ultimately succumbed to his condition four days after the procedure. The experimental therapy, which injected genetically engineered viruses into the child’s liver, carried a high risk of death.

In order to protect the public from the dangers of gene therapy, the FDA and the NIH tightened their monitoring of gene therapy trials.

In addition, the FDA required that scientists notify the agency if their clinical trials cause serious side effects. This is why Wilson was so concerned about the safety of gene therapy for his son.

Since Jesse Gelsinger died from gene therapy, there has been a public outcry about how the drug was developed and whose people are responsible.

The case has raised questions about gene therapy and the role of the institutional review board that approved the trials.

Moreover, the trial’s local institute may have mishandled data pertaining to the use of animals in clinical trials. The death of Jesse Gelsinger has prompted a new regulatory process for gene-therapy trials in the US.

In addition, the Gelsinger family has sued the University of Pennsylvania. While it settled the lawsuit for an undisclosed amount, the university declined to assume any responsibility for Jesse’s death.

After Jesse Gelsinger’s death, the FDA suspended the Penn University’s human research, and Dr. James Wilson admitted to a series of violations. In 2000, the University paid $514,000 to the federal government.

Focus on Easy-to-target Diseases

Gene therapy is becoming a viable treatment option for several diseases. This innovative technique consists of replacing a defective gene with a healthy one.

Its success has been fueled by recent advances in science and technology. Gene therapy has the potential to transform the way we treat disease, develop drugs, and diagnose patients. To date, several gene therapies have been approved by the U.S. Food and Drug Administration.

To achieve its potential, gene therapy must address a wide range of challenges. The success of these therapies will require innovative approaches to technical challenges and robust and scalable manufacturing. In addition, these therapies require a collaborative approach.

Pfizer has demonstrated its commitment to tackling these challenges by establishing partnerships across multiple communities, including regulators, biotechnology companies, and rare disease experts.

While gene therapy is becoming an important part of modern medicine, research and development efforts must be devoted to developing treatments that will benefit the most patients.

Gene therapies can be used to treat a variety of diseases, including inherited and difficult-to-treat conditions. For instance, gene therapy can be used to treat diabetes and other diseases where the treatment of the underlying disease is complex.

For gene therapy to be effective, it must understand disease pathogenesis. Some diseases, such as sickle cell disease, can be successfully treated by using a small number of self-renewing stem cells. However, other diseases, such as postmitotic diseases, require direct delivery of the therapeutic agent.

Ethics of Gene Therapy

The ethical debate surrounding gene therapy is one of the most pressing concerns in modern genetics. For the first time, there has been an extensive debate about the potential uses of this technology before it has been widely available.

This is a unique opportunity for ethical debate to influence the development of a technology from its earliest stages. The debates surrounding other genetic issues have typically occurred after the technologies themselves have been developed.

Gene therapies are expensive. The benefits of a therapy are often decoupled from the costs. Also, there is very little long-term efficacy data available on most of these treatments. That makes the long-term cost-effectiveness argument difficult to make.

However, as public payers become more comfortable with these therapies, they will be more likely to pursue their use. This will require a paradigm shift, and an investment by multiple stakeholders. Ultimately, gene therapies must be implemented responsibly to ensure that they reach patients in need.

While the ethical debate surrounding gene therapy continues, new studies have been conducted in recent years to make the procedure safer.

However, researchers will still have to decide what level of risk is acceptable and who should bear the costs. In the 1990s, scientists rushed to conduct clinical trials on human subjects, driven by overenthusiastic scientists and charitable foundations chasing a cure. Unfortunately, the trials didn’t prove to be as promising as many believed.

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