Introduction

Gene therapy is an innovative medical approach that uses genetic material (DNA or RNA) to treat or prevent diseases. Instead of only addressing symptoms, gene therapy targets the underlying cause of disease by adding, replacing, or fixing genes inside cells. By the end of 2024, there were 33 gene therapies approved around the world [1], including advanced treatments like CAR-T therapies that modify a patient’s own cells to fight cancer. 

Recent approvals include new treatments such as Aucatzyl, designed for patients with certain types of leukemia, and Tryngolza, created to help patients with a rare genetic disorder called lipoprotein lipase deficiency. The number of potential new gene therapies is rapidly growing, with an 83% increase in therapies nearing approval at the end of 2024.[1]

It is important to understand how gene therapy works, but it often can be confusing and difficult to understand. This report provides a comprehensive overview of gene therapy, including early developments, challenges and recent revolutionary breakthroughs. Additionally, it explains the mechanisms of how gene therapy works in practice, describing various techniques such as gene editing, gene silencing and the role of vectors in delivering therapeutic genes. Finally, recognizing the rapid evolution of this field, the report also suggests reliable resources to keep up-to-date with the latest advancements, ensuring readers have the necessary tools to stay informed and engaged with ongoing progress in this exciting healthcare frontier.

Key words

Base Editing: A newer, precise type of gene editing that changes single letters in DNA to correct genetic mistakes.

Cell-Based Gene Therapy: A method where a patient's cells are modified in a lab and then returned to their body to treat diseases.

Clinical Trials: Studies testing new treatments in humans to ensure safety and effectiveness.

CRISPR/Cas9: A powerful tool that acts like molecular scissors to cut and fix DNA precisely, helping correct genetic defects.

DNA: A molecule that carries genetic instructions telling our bodies how to grow, develop, and function.

FDA Approval: Official authorization given by the Food and Drug Administration for new therapies to be used safely in patients.

Gene Editing: Precise methods like CRISPR/Cas9 used to correct specific mistakes or mutations in a person's DNA.

Gene Silencing: Turning off genes that cause harmful effects, preventing them from making problematic proteins.

Gene Therapy: A medical technique used to treat or prevent diseases by changing or replacing faulty genes with healthy ones.

Genetic Disorders: Diseases caused by changes or mutations in a person's DNA.

Immune System: The body's natural defense system, which can sometimes be trained by gene therapy to recognize and fight diseased cells.

Liposomes: Tiny bubbles made of fat that carry therapeutic genes into cells.

Non-Viral Methods: Ways to deliver genes into cells without using viruses, potentially safer and simpler.

Plasmid DNA: Circular pieces of DNA engineered to carry healthy genes into human cells.

Rare Diseases: Illnesses affecting only a small number of people, often targeted by gene therapies.

Retroviral Vectors: Viruses modified in labs to safely insert new genetic material into cells.

Stem Cells: Special cells capable of becoming many different types of cells in the body, useful in gene therapy.

Vectors: Vehicles, often modified viruses, used to deliver healthy genes into human cells during gene therapy.

What is gene therapy & how does it work?

Gene therapy is a revolutionary approach to medicine that involves modifying a person's genetic material (typically DNA or RNA) to treat or prevent disease [2]. It targets the root cause of genetic disorders by correcting faulty genes or introducing new ones [3].

What are genes and how can they cause disease?

Most of our body’s genetic information is stored in 23 paired chromosomes inside the nucleus of our cells. Each chromosome is made up of DNA that stores information to determine our unique characteristics. Specific sections of DNA are called genes. Each person typically gets two copies of each gene from their biological parents. These genes control everything from hair color, to height, to many other traits. As far as we know, humans have between 20,000 and 25,000 genes. [4]

Genes are the blueprints providing instructions on how to make proteins for the body. Proteins play an important role in how our body functions. Unfortunately, these blueprints are not always correct. A gene variant, also known as a gene mutation, is a small change to the DNA within our genes that can alter the instructions for how proteins are built and work.

This can then affect how a person breathes, walks, or digests food. Gene changes can be inherited (passed along from parents), can happen as we age, or can be caused by environmental factors (chemicals and radiation). These genetic changes happen to everyone but sometimes there can be rare changes that cause disease by altering how specific proteins function [4]. When a gene is faulty, it can lead to a missing or malfunctioning protein, causing a genetic disorder [5].

How does gene therapy work?

Gene therapy aims to address the underlying cause of disease, such as changes in our genes. If genes are like the blueprint to our body, gene therapy can fill in missing parts or correct errors in the drawings [4].

Gene therapy approaches:

• Gene addition: This involves inserting a new copy of a gene into cells to help fight a disease or compensate for a faulty gene. For example, if a gene is missing or not working properly, gene addition can provide a healthy copy of the gene to restore normal function [6].

• Gene silencing: This aims to turn off or block the activity of a gene that is causing problems. For example, if a gene is producing a harmful protein, gene silencing can prevent that protein from being made. [6]

• Gene editing: This uses tools like CRISPR/Cas9 to make precise changes to the DNA within a cell, correcting the underlying genetic defect. This technique allows for very specific modifications to the gene, potentially correcting the root cause of the disease [6].

• Cell-based gene therapy: This involves modifying a patient's cells outside the body and then returning them to the patient. This approach is often used for blood disorders or immune system conditions. For example, a doctor can remove immune system cells (cells that are part of your body's natural defense system) or bone marrow cells from your body, modify their DNA, and then re-introduce them to your body [6].
  
  

• RNA therapy: Delivers temporary RNA instructions (mRNA) directly to cells to make therapeutic proteins without permanent DNA changes. Example: COVID-19 mRNA vaccines.[26]
  
  

• Antisense Oligonucleotides (ASOs): Short synthetic molecules that specifically bind to messenger RNA. They temporarily correct gene expression by stopping harmful proteins from being produced. ASOs need to be regularly administered, typically every few months.[26]

Types of gene therapy administration:

• In vivo gene therapy: Genetic material is introduced directly into the patient. This method can involve injections into specific tissues or the bloodstream.[26]

• Ex vivo gene therapy: Patient cells are collected, genetically modified outside the body, and returned. Often used for blood or immune system disorders.[26]

Vectors in gene therapy:

A gene can't easily be inserted directly into your cells. Rather, it usually is delivered using a carrier called a vector [7]. The most common gene therapy vectors are viruses because they can recognize certain cells and carry genetic material into the genes of those cells [7]. Researchers modify these viruses by removing the genes that cause disease and replacing them with genes needed to stop disease [7].

While viruses are the most common vectors, other types are being studied in clinical trials, including:

• Stem cells: These are special cells that can develop into many different types of cells in the body. For gene therapy, stem cells can be altered or corrected in a lab to become cells to fight disease [7].

• Liposomes: These are tiny bubbles of fat that can carry the new, therapeutic genes to the target cells and pass the genes into the DNA of your cells [7].

If you're living with - or caring for someone with - a specific condition and would like us to create a tailored guide for your community, we'd love to hear from you. Reach out to us at info@allmyhealth.io, and let's discuss how we can help.

History of gene therapy

The concept of gene therapy first emerged in the 1960s and 1970s [8]. Since then, the field has experienced both significant milestones and setbacks. To better understand its evolution, let's explore the history of gene therapy through these key periods:

Early developments (1960s - 1980s)

• 1962: The foundation of gene therapy was established by Professor William Szybalski, who showed that genetic mutations could be fixed by adding new DNA to animal cells [9].

• 1970s: Scientists began exploring ways to add healthy genetic material to mammalian cells which are tiny building blocks that make up the bodies of mammals, opening exciting possibilities for treating inherited diseases [10].

• 1972: Researchers Friedmann and Roblin proposed the innovative idea of using healthy DNA to replace faulty DNA in people with genetic disorders [8].

• 1975: The Asilomar Conference brought together scientists, journalists, and government officials to discuss ethical issues related to gene therapy. The conference established important guidelines to ensure safe and responsible research [9].

• 1980s: Significant advancements occurred in developing methods for gene transfer, including retroviral vectors, tools that can efficiently insert new genes into mammalian cells [10].

Clinical trials and setbacks (1990s - Early 2000s)

• 1990: The first approved gene therapy trial took place, successfully treating a four-year-old girl with adenosine deaminase deficiency (ADA), a rare genetic disorder affecting her immune system. This was a crucial step in moving gene therapy from the lab to real-world patient care [11].

• 1999-2000: Unfortunately, the field experienced significant setbacks. One patient tragically died due to an unexpected immune response to the treatment. Additionally, in two other clinical trials in the UK and France, five out of 20 patients developed leukemia because of unintended genetic changes. These events led to increased scrutiny, safety concerns, and temporarily slowed gene therapy research [9].

Recent breakthroughs and approvals (Mid-2000s - Present)

• 2000s: Following these setbacks, the FDA and NIH introduced new safety guidelines, ensuring safer and more effective gene therapy trials [9].

• 2010s: The emergence of advanced gene-editing technologies like CRISPR/Cas9 transformed gene therapy by offering precise and efficient methods to correct genes [9].

• 2017: The FDA approved Luxturna, the first gene therapy to treat a rare inherited eye disease that can lead to blindness. In the same year, two gene therapies for certain types of cancer, Kymriah (for acute lymphoblastic leukemia) and Yescarta (for large B-cell lymphoma), were also approved, highlighting the growing success of gene therapy treatments [7].

• 2023:The FDA approved the first CRISPR-based therapy for sickle cell disease, offering a groundbreaking treatment option for patients [9].

• 2024: ​The FDA approved nine new cell and gene therapy products, marking a significant milestone in the field [12].

The history of gene therapy showcases remarkable resilience and progress. Despite early challenges, ongoing innovation has led to safer, more effective treatments, offering hope and improved quality of life for many patients and their families [6].

Considerations and limitations

Gene therapy represents a groundbreaking approach to treating diseases by directly modifying genetic material within cells. Despite its potential, several challenges and considerations must be managed effectively to ensure safety and efficacy.

Below are some key considerations and challenges associated with gene therapy that highlight the complexities and ethical responsibilities involved in its development and clinical application:

• Immune reactions: The body can develop antibodies against gene therapy vectors, such as Adeno-associated virus (AAV), complicating repeat treatments. To manage this, temporary immunosuppressive medications may be given alongside treatment. [26]

• Permanent vs. temporary effects: Gene editing or addition typically has permanent effects, meaning the treatment remains active for the long term. RNA-based approaches (including ASOs) are temporary and often require repeat dosing.[26]

How to stay updated on the latest advancements in gene therapy?

If you would like to stay informed about the latest advancements in gene therapy, here are some websites and resources you can refer to:

• National Institutes of Health (NIH): A leading U.S. medical research agency, the NIH offers extensive information on various health topics, including regenerative medicine and cell therapy. Their resources include educational materials, research updates, and access to clinical trial databases.[5]
  https://www.nih.gov/

  
  

• Genetic and Rare Diseases Information Center (GARD): Part of the NIH, GARD offers detailed information on rare and genetic diseases. Visitors can explore educational materials, locate specialists, and learn about new or ongoing clinical trials related to cell and gene therapies.[13]
  https://rarediseases.info.nih.gov/ 

  
  

• Mayo Clinic: Renowned for clinical care and research, the Mayo Clinic provides comprehensive, patient-friendly information on a wide range of conditions. Their website covers stem cell therapy, transplantation options, and ongoing clinical research. [3]
  https://www.mayoclinic.org/

  
  

• American Society of Gene & Cell Therapy (ASGCT): This website provides comprehensive information about gene and cell therapy, including patient education resources, clinical trial information, and the latest news and research. ASGCT also hosts scientific meetings, as well as patient meetings, and publishes updates on the rapidly evolving field. [11]
  https://www.asgct.org/ 

  
  

• Yale School of Medicine: Yale’s website features articles and updates on advancements in gene and cell therapies, with a particular focus on rare diseases. Learn about cutting-edge research from one of the world’s leading academic institutions. [14]
  https://medicine.yale.edu/news-article/the-future-of-gene-editing-treatments-for-rare-diseases/

  
  

• ScienceDaily: ScienceDaily aggregates the latest research findings and news articles from scientific journals. Its gene therapy section covers both gene and cell therapy breakthroughs, keeping you up to date on cutting-edge discoveries. [15]
  https://www.sciencedaily.com/news/health_medicine/gene_therapy/

  
  

• BioPharma Dive: An industry-focused site covering biotech, pharma, and life sciences news. BioPharma Dive reports on business trends, FDA updates, and clinical trial results related to gene and cell therapy. [16]
  https://www.biopharmadive.com/topic/gene-therapy/

  
  

• AllMyHealth: Provides comprehensive, curated content weekly as well as extra resources for rare disease communities, improving access to specialized news, research, clinical trial information and support for those who need it most. [17]
  https://www.allmyhealth.io/ 

These resources provide valuable information on gene therapy research, clinical trials, patient support, and educational materials.

Conclusion

Gene therapy is a rapidly evolving field with immense potential for future advancements. Researchers are exploring new gene editing technologies, such as base editing, which allows for even more precise modifications to DNA [14].They are also developing new delivery systems, including non-viral methods, to improve the safety and efficacy of gene therapy. [14]

While challenges persist, ongoing research and development continue to propel progress, bringing renewed hope to patients and their families. In the future, we may see gene therapies being used to treat a wider range of diseases, including more common conditions like cancer, heart disease, and neurological disorders [16]. Gene therapy also holds promise for preventing diseases before they even develop.

By staying informed, individuals can make empowered decisions about their healthcare and engage with the exciting advancements this field has to offer. Remember, support and resources are available to help guide you every step of the way.

If you're living with - or caring for someone with - a specific condition and would like us to create a tailored guide for your community, we'd love to hear from you. Reach out to us at info@allmyhealth.io, and let's discuss how we can help.

References

1. Gene, Cell, & RNA Therapy Landscape Report
https://www.asgct.org/global/documents/asgct-citeline-q4-2024-report.aspx 

2. Gene Therapy - National Human Genome Research Institute https://www.genome.gov/genetics-glossary/Gene-Therapy 

3. Transforming your care
https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619#:~:text=Gene%520therapy%20aims%20to%20fix,better%20able%20to%20fight%20disease. 

4. Gene Therapy Basics
https://patienteducation.asgct.org/gene-therapy-101/gene-therapy-basics 

5. National Human Genome Research Institute
https://www.genome.gov/genetics-glossary/Gene-Therapy#:~:text=Gene%20therapy%20is%20a%20technique,healthy%20version%20of%20that%20gene.

6. What Are Genetic Therapies? | NHLBI, NIH
https://www.nhlbi.nih.gov/health/genetic-therapies 

7. Gene therapy - Mayo Clinic
https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619 

8. National Library of Medicine
https://pmc.ncbi.nlm.nih.gov/articles/PMC9296588/#:~:text=The%20earliest%20conceptual%20history%20of,hematopoietic%20stem%20cells%20(HSC). 

9. Gene therapy history | GenePossibilities HCP
https://www.genepossibilitieshcp.com/gene-therapy-overview/gene-therapy-history

10.  National Library of Medicine
https://pmc.ncbi.nlm.nih.gov/articles/PMC5823056/ 

11. Timeline of Gene and Cell Therapy - ASGCT
https://www.asgct.org/about/timeline-history 

12. Biopharma
https://www.biopharmiq.com/post/2024-breakthrough-9-new-cell-and-gene-therapies-approvals 

13. Resources for Rare Disease Patients and Advocates
https://ncats.nih.gov/resources/for-rare-disease-patients-and-advocates 

14. The Future of Gene-Editing Treatments for Rare Diseases - Yale School of Medicine
https://medicine.yale.edu/news-article/the-future-of-gene-editing-treatments-for-rare-diseases/ 

15. Gene Therapy News - ScienceDaily
https://www.sciencedaily.com/news/health_medicine/gene_therapy/ 

16. Gene Therapy News | BioPharma Dive
https://www.biopharmadive.com/topic/gene-therapy/ 

17. All My Health
https://www.allmyhealth.io 

18. What is Gene Therapy? - FDA
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy

19. Gene Therapy | Boston Children's Hospital
https://www.childrenshospital.org/treatments/gene-therapy

20. Gene Therapy Downloadable Resources & Organizations - Genehome
https://www.thegenehome.com/resources

21. Gene therapy resources for patients and caregivers ∣ Vertex Connects
https://www.vertexconnects.com/tools-and-resources

22. Gene Therapy Hub - Evernorth Health Services
https://www.evernorth.com/gene-therapy-information-hub

23. Alliance for Regenerative Medicine
https://alliancerm.org/

24. The future of gene therapy - Evernorth Health Services
https://www.evernorth.com/articles/gene-therapy-changing-landscape

25. Gene Therapy Approaches
https://patienteducation.asgct.org/gene-therapy-101/gene-therapy-approaches

26. Dr Stephen Gray, Empowering Patients 2025: A Cell and Gene Therapies Summit, American Society of Gene and Cell Therapy
https://www.asgct.org/asgct-events/march-2025/empowering-patients-2025-a-cell-and-gene-therapie?_gl=1*18vpmi*_ga*MTMzNTkyMzA5Mi4xNzI1ODkwMjA3*_ga_Q37QKR6TCJ*MTcyODA3NDE3MS4xMTMuMS4xNzI4MDc1NjQ4LjAuMC4w&_ga=2.151380081.954937067.1727703854-1335923092.1725890207