February 24, 2024

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What is the current clinic status of global gene therapy?

What is the current clinic status of global gene therapy?


What is the current clinic status of global gene therapy?

The concept of gene therapy was proposed in the early 1970s. The original concept was to introduce a normal gene to replace a mutant gene.

Although there are more alternative methods, such as gene editing and base editing , it is still is one of the main strategies on which we rely heavily.


In 2012, Europe approved Glybera, which is the first gene therapy product in a western country and the world’s first gene therapy for genetic diseases.

Although Glylbera was not a commercial success, it opened the door to gene therapy.

In the ensuing years, a number of gene therapy products flooded the market, with Strimvelis being approved in Europe in 2016, and CAR-T therapies ( Kymriah and Yescarta ) and Luxturna being granted US Food and Drug Administration ( FDA ) approval in 2017, respectively. approval.


According to data from Frost & Sullivan, since 2015 , the global gene therapy industry has developed rapidly.

By 2016 , the global and domestic gene therapy market sizes were USD 50.4 million and RMB 15 million respectively; in 2020 , the global gene therapy market will increase to reach USD 2.08 billion.

It is estimated that in 2025 , the global market and the domestic market will reach nearly 30.54 billion US dollars and 17.89 billion yuan respectively.

Gene therapy has become the third industrial revolution of biomedicine after small molecule drugs and antibody drugs.




The development stage of gene therapy

Gene therapy has gone through the following four stages from its invention to its initial application and its current vigorous development:


What is the current clinic status of global gene therapy?



Basic research stage (1909-1973)

First, Wilhelm Johannsen coined the term “gene,” and then about half a century later, Francis Crick and James Watson discovered the double helix structure of DNA.

The fundamentals of gene transfer in bacteria were discovered in the 1960s and subsequently developed into eukaryotic transfection techniques.

By the 1970s, the use of restriction enzymes and ligases formed the basis for genetic manipulation, and recombinant DNA technology enabled researchers to introduce selected therapeutic genes into engineered vectors.

With the discovery of the ability of viruses to transfer genetic material, viral vectors have emerged as a promising tool for efficient gene transfer.

These technological advances allow scientists to create gene therapy vectors that transfer specific genetic material into target cells.


Early gene therapy clinical practice (1989–2003)

The first clinical practice of gene therapy began in 1989, when a retrovirus was used to express the neomycin resistance marker on tumor-infiltrating lymphocytes, which was used to track infiltrating lymphocytes in melanoma immunotherapy .

In 1990, scientists at the University of Pennsylvania conducted the first successful clinical trial of gene therapy on a four-year-old girl, Ashanti Desilva.

She was diagnosed with severe combined immunodeficiency ( SCID ), and researchers used a retroviral vector to transfer a normal copy of adenosine deaminase ( ADA ) to her T cells. She is now able to live a normal life.


However, the use of viral vectors is accompanied by some adverse events, such as insertional mutations and immune reactions, which hinder the progress of clinical gene therapy.

In 2000, European researchers in Paris reported a successful clinical trial of gene therapy for X-linked SCID.

However, five of the 20 treated children later developed leukemia due to activation of an oncogene following the introduction of the transgene by the vector.

Meanwhile, in 1999, Jesse Gelsinger, an 18-year-old boy diagnosed with a rare metabolic disease, volunteered as a patient to receive a gene therapy encoding an enzyme called ornithine transaminase.

Unfortunately, however, he died of massive coagulation disorders and subsequent multi-organ failure, becoming the first death patient of gene therapy. Although these setbacks have slowed gene therapy progress, they have also demonstrated gene therapy’s potential and its bright future.


Prosperous development stage (2003-2022)

The first in vitro gene therapy product, Strimvelis, was approved by the EMA in 2016.

In 2017, the FDA approved two chimeric antigen receptor ( CAR ) T-cell products, Kymriah and Yescarta, a key milestone that paved the way for future products.

Luxturna is the first in vivo AAV gene therapy product approved by the FDA for Leber congenital amaurosis ( LCA ), and was approved in 2017.

In 2019, the FDA approved the most expensive drug to date, Zolgensma, an AAV product for children with spinal muscular atrophy.

The number of approved gene therapy products is increasing every year.


Future Development (2022–2025)

Based on previous clinical trials and currently approved products, this promising field of medicine appears to be moving faster than ever, with dozens of new product approvals expected in the near future.

We are gradually integrating gene therapy into the broader field of disease treatment.


What is the current clinic status of global gene therapy?





Clinical overview of cancer gene therapy

Current clinical applications of gene therapy can be divided into three main areas: cancer, genetic disorders, and infectious diseases.


What is the current clinic status of global gene therapy?


While gene therapy is considered a treatment for certain genetic diseases, cancer is the most common disease for which gene therapy is used.

From 2010 to 2020, cancer-related clinical trials accounted for the majority of all research.

Hematological cancers are the most studied cancers, followed by gastrointestinal and nervous system cancers.


What is the current clinic status of global gene therapy?


CAR-T cells are one of the best-known and most successful gene therapy applications in immunotherapy.

Judging from the current clinical trials for cancer, most trials are in the first stage.

The number of phase 2 clinical trials is also high, but only a few have followed up with phase 3 trials.



To date, several gene therapy products have been approved for the treatment of cancer, including gendicine, oncorine, rexin-G, imlygic, delytact, and eight CAR-T cells, including kymriah, yescarta, tecartus, breyanzi, abecma, ARI-0001, carteyva and carvykti.




Clinical Overview of Gene Therapy for Inherited Diseases

Unlike cancer, most of these diseases, such as thalassemia, Deschene muscular dystrophy ( DMD ), and cystic fibrosis, are hereditary. More than half of clinical trials focus on metabolic disorders, eye diseases and coagulation disorders. Further, the most clinically tested genetic diseases are SMA, DMD, hemophilia B, ADA-SCID, and β-thalassemia.




There is a higher proportion of phase 3 clinical trials for genetic diseases than for cancer.

LCA, SMA, ATTR amyloidosis, primary hyperoxaluria, amyloid neuropathy, DMD, lipoprotein lipase deficiency, familial chylomicronemia syndrome, and hypertriglyceridemia are phase 3 trials Inherited diseases being studied.

In addition, there are two Phase 4 clinical trials involving two FDA- and EMA-approved gene therapy products, Spinraza and Zolgensma, for the treatment of SMA.


Although the total number of clinical trials for genetic diseases is less than for cancer, the number of products currently approved for genetic diseases is higher ( 20 vs. 13 ).

To date, products have been approved for ADA-SCID, DMD, SMA, LCA, Thalassemia B and multiple metabolic diseases.




Clinical overview of infectious diseases and other gene therapy

There is a constant struggle to find cures for some of the worst infectious diseases, such as AIDS or malaria, and gene therapy is no exception.

Although they represent a small fraction of gene therapy clinical trials, 29 trials for COVID-19 have been launched since December 2019 as the pandemic emerged.

AIDS, COVID-19, malaria, Ebola, hepatitis C, HPV infection and hepatitis B are the infectious diseases with the most clinical trials.


Most clinical trials use vaccination strategies to induce immunity to corresponding diseases.

There are only a few gene therapies at an advanced stage, that is, gene therapy using DNA as a vector for HBV.

Judging by the approved products, gene therapy strategies still have a long way to go in effectively addressing infectious diseases.


In addition, in addition to cancer, genetic diseases, and infectious diseases, research on gene therapy has also been used in peripheral vascular disease, osteoarthritis, diabetic retinopathy, macular degeneration, coronary artery disease, myocardial ischemia and infarction, diabetic neuropathy, allergy rhinitis, heart failure, and hypertrophic scarring.



Regional Distribution of Gene Therapy Clinical Trials

In the early 1990s, the National Institutes of Health conducted the first successful clinical trials of gene therapy. Although the U.S. has conducted more gene therapy clinical trials than any other country since then, China was the first to approve the first commercially available gene therapy product ( Gendicine ). In the late 1990s, several countries in Europe were among the first to implement gene therapy.




Currently, the United States and China dominate gene therapy clinical trials, accounting for about 80% of all trials.

Several other countries have excelled in this promising field in recent years, including the UK, France, Spain and Germany.

There are an increasing number of ongoing clinical trials in collaboration with institutes or universities in several countries. The number of gene therapy clinical trials doubled between 2010 and 2020.





Gene therapy has been in clinical practice for about thirty years.

Looking at the development trend of gene therapy in the last century, we have entered a new era, as evidenced by the increasing number of gene therapy products approved in the past decade.

And with breakthroughs in the development of genetics and biotechnology, such as CRISPR-CAS gene editing, the types of diseases that can be treated by gene therapy have expanded.


The ten-year trend analysis of gene therapy clinical trials shows that although gene therapy is mainly used for cancer and genetic diseases, clinical trials for many infectious diseases including AIDS, malaria and human papillomavirus have entered the late stage of clinical research.

In the past 10 years, in vitro gene therapy has made some progress, and there are currently many pipelines, and in vivo gene therapy will usher in a new development climax in the next decade.









1. Gene therapy clinical trials, where do we go? An overview. Biomed Pharmacother. 2022 Sep;153:113324

What is the current clinic status of global gene therapy?

(source:internet, reference only)

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