What is gene therapy?

Gene Therapy: A complete guide

What is Gene Therapy? What are the applications of Gene Therapy?

Gene therapy is the introduction, removal, or change in genetic material specifically DNA or RNA into the cells of a patient to repair or change a gene to treat a specific problem.

As per the Human Genome Project humans are reported to have about 20,000-25,000 genes.

Genes are made up of DNA that are like blueprints to build enzymes or protein that do the work in our body

Most of us have two copies of each gene that we inherit from our parents, they are the building blocks of our physical structure, from the color of our eyes, our athletic abilities to our immune system

But, What happens when genes are not built correctly?

A small irregularity in the DNA of the gene can change the way our proteins are produced and the way they function.

This can impact the way we talk, breathe, digest, certain food. 

Our genes are mutating all the time as a result of several chemical processes that are happening in our cells or maybe external influences like UV light

We can also inherit certain mutations from our parents which can lead to certain genetic diseases like Thalassemia and Muscular Dystrophy.

This is where Gene Therapy comes in, Gene Therapy can fill the missing drawing in the gene blueprints and help us treat several genetic disorders.

If we have to define gene therapy in standard words

Gene Therapy Definition:

Gene therapy is a broad term that encompasses different techniques that facilitate the construction and delivery of genetic material that augments, alters or controls the inherent genetic defect causing disease pathology

Gene therapy has been quite a buzz word in the healthcare community for being one of the wonder sciences that promises to be the panacea or cure of all diseases.

In India the Central Drugs Standard Control Organization (CDSCO)  has classified gene therapy as a “new drug “, the potential of which is still to be explored.

So let’s dig deep into one of the most promising fields of biomedicine

Gene Therapy: A Complete Guide

  1.   History of Gene Therapy
    1. History of gene therapy in India 
    2. Potential of Gene Therapy in India 
  2. Types of Gene Therapy 
  3. Gene Therapy Vectors
  4. Applications of gene therapy,
  5. Controversy around Gene Therapy 

History of Gene Therapy 

The Gene Therapy press conference held on September 13, 1990. From left to right: R. Michael Blaese, M.D., W. French Anderson, M.D., and Kenneth Culver,. M.D. 1990
The Gene Therapy press conference held on September 13, 1990. From left to right: R. Michael Blaese, M.D., W. French Anderson, M.D., and Kenneth Culver,. M.D. 1990

Gene Therapy is certainly an advanced science, But it has been around with us for quite a  long time now.

The history of Gene Therapy starts in the 1970s approximately 100 years after the discovery of DNA by Friedrich Miescher in 1869.

History of Gene Therapy Year 1960-2000

  1. 16th December 1961: Lorraine Kraus reports the first successful incorporation of functional DNA directly into a mammalian cell

  2. 10th December 1966: Stanfield Rogers published evidence that  virus could be used for gene transfer

  3. 1970: First Gene Therapy on Human by Stanfield Rogers on 3 german sisters suffering from hyperargininemia. The therapy failed.

  4. 3rd March 1972: Friedmann and Roblin published a paper (“Gene therapy for human genetic disease?”) about the potential of gene therapy to treat genetic diseases. 

  5. May 1983: Mann, Mulligan, Baltimore Create the first retrovirus that can be used as a vector for Gene Therapy

  6. 19 Sep 1985: Technique for accurate transfer of corrective DNA in the human genome was published.

  7. January 1990: First-time scientists prove the concept of gene therapy by human trials.

  8. September 1990: 4-year-old girl Ashanti DeSilva becomes the first patient to be successfully treated with Gene Therapy

  9. 17th September 1999: The first patient to die during trials of gene therapy, resulted in a major set back and criticism for the field.

  10. 2000: 2 french boys suffering from SCID reported to be cured by Gene Therapy

History of Gene Therapy Year 2000-2020

PPMD’s Annual Advocacy Conference 2019
PPMD’s Annual Advocacy Conference 2019
  1. 16th Oct 2003: China becomes the first country to approve commercial gene therapy. 

  2. 29th Jun 2008: Gene Therapy used to develop immunotherapy for HIV treatment 

  3. 2009: Blind child suffering from eye disorder gains vision using gene therapy

  4. January 2010: Gene Therapy successfully treats beta-thalassemia

  5. July 2012: Gene Therapy approved for treating patients with familial lipoprotein lipase deficiency

  6. October 2015: Oncology gene therapy approved in Europe and the USA

  7. 21st Jun 2016: National Institutes of Health approves first clinical trial using the new gene-editing tool CRISPR/Cas 9 

  8. 2nd Mar 2017: Gene Therapy cures sickle cell disease in a patient

  9. 16th Nov 2017: For the first time a patient receives therapy involving gene editing  inside the body 

  10. 23rd Nov 2018: Europe approves gene therapy to treat vision loss due to genetic disorder

  11. December 2018: Chinese Scientist He Jiankui reports creating the first genetically edited babies (Twins by the name Lulu and Nana)

    The twins were claimed to be resistant to HIV. The experiment was conducted without proper approvals and received great criticism for violating the ethics

    This experiment raised several red flags and made everyone more worried about the possible ill use of the technology

  12. 2020: Clinical trial ongoing to treat coronavirus using DeltaRex-G Gene Therapy

History of gene therapy in India

Gene therapy. in India
Rohan Kamat, Co-founder of Viravecs, A biotech startup working on gene therapy in India
Image Src: The Print

India has a large burden of genetic disorders and unmet medical needs and gene therapy can prove to be a turning point in the treatment of such disorders

But, Gene therapy in India is still a nascent field. The journey of Gene Therapy in India started in the 1990s

  1. 1998: The first center dedicated to the research of gene therapy in India was ACTREC, Mumbai.

    The center was involved with gene therapy studies related to the treatment of head and neck cancer using viral vectors.

  2. 2002: Debi Sarkar at University of Delhi established a research lab that focused on creating better hybrid vectors, which could be used in gene therapy

  3. 2004:  Dr. Subrata Banerjee at  Saha Institute of Nuclear Physics, Kolkata, WB worked on gene therapy for hematological disorders

  4. 2005: Dr. Kumaravel Somasundaram at Indian Institute of Science, Bengaluru worked on gene therapy for cervical cancer

  5. 2010: Dr.Jayandharan and Dr.Sanjay start an independent lab Center for stem cell research.

    They focused on research of gene therapy on hemophilia, leukemia, and bone disorders.

  6. 2012: Gene therapy lab was established in Vellore institute of technology that focused on gene therapy for leukocyte adhesion deficiency

    Dr.Rupesh Dash from Institute of Life Sciences, Bhubaneswar started working on gene therapy for prostate cancer

  7. 2013: Dr. Arkasubhra Ghosh from Narayana Nethralaya, Bengaluru started working on adenosine associated viral vectors 

  8. Starting with just 1 Lab researching gene therapy in 2000 in 2013 India had 10 Labs working on gene therapy.

    Currently we have several labs working on gene research which promises good results for India.

Potential of Gene Therapy in India

Gene Therapy in India

Every year millions of Indians are affected by inherited monogenic or complex diseases and have limited or no treatment options.

A number of these genetic disorders are associated with life-long disability and are a significant economic burden to the society and the healthcare system.

India has a large burden of monogenic diseases.

These include hemophilia, thalassemia, sickle-cell anemia certain forms of muscular dystrophies, retinitis pigmentosa, PID in children, lysosomal storage disorders such as Pompe disease, Gaucher’s disease, haemangioma, cystic fibrosis, etc.

In India, 

  • hemophilia A is reported in 11,586 patients although the prevalence is estimated to be around 50,000 patients.

  • Similarly, there is a large burden of about 100,000 β thalassemia patients,

  • around 150,000 sickle cell patients, 

  • 500,000 (Duchenne Muscular Dystrophy) for muscular dystrophy and a

  • higher incidence of 1 in 4000 for retinal dystrophies.

  • Considering the international estimate of 6% to 8% of the population is affected by rare diseases,

    approximately 72 to 96 million people in India can be expected to be affected by some form of a rare disease, which is of major concern to the health care sector.

  •  India also has a huge burden of multifactorial diseases such as cancer, with around 2.25 million patients affected by the disease and approximately, 7,84,821 succumbing to it every year.

Therefore, it is imperative to establish a safe, novel, targeted treatments for all such conditions in Indian patients.

Having treatments like gene therapy would prove a big aid for India and would certainly also make India one of the biggest markets for gene therapy in the future.

Read about the guidelines of gene therapy in India

Types of Gene Therapy

There are primarily two types of gene therapy 

  1. Germ Line Gene Therapy

  2. Somatic Cell Gene Therapy 

Germ Line Gene Therapy

Germ-line gene therapy is applied to germline or gametes which can be transmitted vertically across generations.

The concept of germ-line gene therapy is to introduce gene-modified cells into the germline (Like introducing genes in eggs and sperms.

This makes the traits gained by the therapy heritable to the next generation.

Germline or in utero gene therapy is prohibited in India, due to ethical and social considerations. 

But it’s not just India, Germline gene therapy is prohibited in 40 countries apart from The US and China because of safety, ethical and technical issues.

Think about it, If you are given a chance to program your to be born child and you can add or delete certain traits in your child (Gene Enhancement), Would you not do it?

Probably not but the ethical issues and the potential risk associated with this line of treatment makes sense.

Somatic Cell Gene Therapy 

Somatic Gene Therapy
Somatic Gene Therapy

The only and more socially acceptable approach because it affects the targeted cells/tissue/organs in the patient, and is not passed on to subsequent generations.

This also includes genome modification as exemplified by CRISPR-related and other technologies or epigenetic modulation by gene therapy approaches with similar effects.

Therapeutic gene cells are transferred to somatic cells which can help a person treat his/her medical condition.

The alterations or corrections done by this type of therapy is not transferred to the next generation.

Somatic gene therapy has two further categories: ex vivo gene therapy and in vivo gene therapy

Ex Vivo Gene Therapy:

Cells obtained from an individual are genetically modified/corrected outside the body followed by transplantation into the same or a different individual

If during the clinical trials involving ex vivo gene therapy cell taken from the person are harvested and genetically modified with or without expansion in the laboratory, the final modified cell is considered Gene Therapy Product (GTP)

A gene therapy product (GTP) is thus defined as any entity which includes a nucleic acid component being delivered by various means for therapeutic benefit.

The first successful gene therapy that treated a human was ex vivo gene therapy.

The therapy was performed on a 4-year-old girl Ashanti DeSilva for treating a deficiency of enzyme Adenosine deaminase.

In Vivo Gene Therapy

The gene of interest is delivered directly to target cells/tissues/organs in the patients. Many tissues are potential targets for this approach.

These include liver, pancreas, muscle, heart, skin, spleen, lung, brain, bone marrow, eye, and others.

In Vivo Gene delivery can be carried out by viral or non- viral vector systems.

It can be the only option for patients or conditions where individual cells can not be cultured outside the body (Eg. Brain Cells)

Gene augmentation, correction of mutation by gene editing, silencing of a dominant mutation can be all considered as GTP

In Vivo gene therapy is used to treat cystic fibrosis by in vivo replacement of defective gene by Adenovirus Vector 

Gene Therapy Vectors 

Gene Therapy in India
Adenovirus, One of the viral vector used in gene therapies

There are two types of vectors 

  1. Viral Vectors 

    1. Retrovirus
    2. Adenovirus
    3. Adeno Associated Virus
    4. Herpes Simplex Virus

  2. Non-Viral Vectors 

    1. Pure DNA Construct

    2. DNA molecule conjugates

    3. Lipoplexes

    4. Human Artificial Chromosome 

What is an ideal vector?

An ideal vector should target the right cell, integrate genes in the cells, activate the gene, and avoid any side effects.

But unfortunately there are no universal vectors, Though some of them might be used more often.

Why are viruses used as vectors?

Viruses attack your cell by introducing their genetic material into our cells as part of their replication cycle. This phenomenon is used by researchers in their advantage.

So viruses are effective tools to transfer any kind of genetic material we wish to transfer in our body. In place of harming us we use them to treat ourselves.

Applications of gene therapy


Gene Therapy is still a nascent field and its application are being explored,

A lot of clinical trials are being conducted to prove the efficacy of gene therapy,

But only a few of the gene therapy and gene therapy products are available commercially.

Applications of gene therapy have shown promises for Cancer, infectious diseases, cardiac disease, neurological disorders, and some inherited conditions.

Gene Therapy for Cancer

Cancer involves cells that divide uncontrollably which destroys tissues and leads to vital harm.

The treatment of cancer using gene therapy is being done by

  • Introducing specific genes in our body that suppresses tumorIntroducing genes that cause cell death or apoptosis

  • When the cancer cells grow to a certain size they require additional vasculature the continued growth which they achieve by angiogenesis.

    Gene therapy introduces genes that are designed to inhibit angiogenesis.
  • Immunotherapy, Gene therapy is being used to treat cancer by strengthening a person’s immune system

    several gene therapies have an immune response as their target which helps produce more fighting cells

Gene therapy is being used for

glioblastoma, metastatic melanoma, head and neck cancer, non-small cell lung cancer, prostate cancer, renal cell cancer, and colorectal cancer.

Gene Therapy for Neurological Disorders

Currently, Alzheimer’s, amyotrophic lateral sclerosis (ALS), metachromatic leukodystrophy (MLD), Batten disease  and Parkinson’s diseases can be treated using gene therapy

Alzheimer’s disease is caused by a deficiency of dopamine in the brain. Using ProSavin we can treat Alzheimers.

ProSavin is delivered in the brain using a lentivirus vector, ProSavin basically contains genes that code for the 3 enzymes that are required to produce dopamine.

Gene Therapy for Inherited Diseases 

Gene therapy can be used to replace a missing/defective gene or express missing biological factors, protein or enzyme caused by inherited diseases like
Gene therapy for Hemophilia, gene therapy for Cystic Fibrosis, gene therapy for Inherited Retinal Degeneration, SCID

On 19th December 2017, A 9-year-old boy gained vision after gene therapy,

The American Academy of Ophthalmology reported the boy suffering from Leber congenital amaurosis (LCA) a hereditary disorder and he was able to gain his vision back within a month of gene therapy.
The US FDA approved this treatment LUXTURNA to treat this disease.

LUXTURNA provides a working RPE65 gene that replaces the mutated RPE65 that causes blindness.

Gene Therapy for Infectious Diseases

Several gene therapy vaccines are being made to target infectious diseases such as

Tuberculosis, HIV, Influenza, and Malaria 

HIV treatment trials

In a gene therapy study involving 74 patients with HIV, The patients were given anti-HIV ribozyme (OZ1) or placebo.

The results showed that the effect or virus had lowered for patients who were given OZ1, lymphocyte counts were more in patients who received OZ1.

Such therapeutic vaccines have the potential to safeguard the immune system and reduce lifelong treatments for diseases like HIV.

Controversy around Gene Therapy 

Gene Therapy sure promises a great deal of benefits in the field of biomedicine but there are several obstacles in performing gene therapy.

The controversy or obstacles around the application of gene therapy are broadly under two categories Scientific or Safety Concerns and Ethical Concerns 

Scientific Concerns 

  • Viral vectors can trigger an immune response

    Gene Therapy involves the use of viruses to transport the required gene sequence in the patient’s body,

    These viral vectors may activate the body’s immunological defense that is used to tackle infections in our body.

    For example, Adenoviral vectors are highly immunogenic of all vectors and they can have extreme effects on our body.

    Due to the immune response of this vector a young man Jesse Gelsinger lost his life while undergoing a gene therapy experiment in 1999.

  • May lead to Mutagenesis or Cancer

    When viruses infect us normally they are restricted to certain tissues depending upon the route of transmission,

    But genetically modified vectors do not have this limitation.

    This nature of genetically modified vectors can lead them to unwanted uptake by cells of different organs that were not targeted.

    Random insertion of this vector can lead to mutagenesis in different cells and cancer

    In a 2003 experiment while treating 5 patients with gene therapy for an immunodeficiency disease 4 out of 5 were successfully treated but of these 4 patients one developed cancer

  •  Gene editing can lead to unintended genetic consequences

    The gene-editing technology can sometimes misdirect itself to different places in the genome and make similar genetic changes to regions that were not the intended target

    This can lead to unintended genetic consequences like turn off of a gene that was really important for body functioning

  • Fear that it may lead us in being biologically different as a species

    Gene editing and different gene therapies may lead to mutations that can make us biologically different as a specie from the way we have been for many generations

Ethical Concerns

Chinese researcher He Jankui
Chinese researcher He Jankui who unethically produced worlds first genetically altered baby
  • Fear of its negative potential

    Gene-editing tools like CRISPR/Cas 9 have made it really easy for researchers and scientists to edit genes.

    While gene editing applications to treat a certain genetic disorder might sound right, Use of gene editing for gene enhancement is a concern.

    Specially germline gene therapy that makes the changes done by gene therapy transferable to the next generation,

    Which means we can design our babies the way we want them to be.

    This type of gene enhancement can have serious repercussions that can disrupt the whole human society

    Let’s look at a case study

    In November 2018 Chinese researcher He Jankui reported that he had produced genetically altered human babies.

    He Jankui misleadingly implanted gene editing embryos into two women one of which gave birth to twin girls Lulu and Nana.

    While the world was still debating the topic of gene therapy this Chinese scientist actually went ahead and did it.

    This particular incident baffled the whole world as this experiment was wrong on multiple levels,

    A thing to note is that during the experiment He Jankui did not introduce gene in the embryos to treat a genetic disease but to gain future immunity from potential infectious disease (HIV)

    This means it’s in a way an early form of genetic enhancement that frightens a lot of people around the world.

    He Jankui also confirmed about there being a third genetically altered baby details of which are not known.

    In December 2019 He Jankui was sentenced to 3 years of Jail.

    Considering the political practice of China we might never know what happened to Lulu and Nana.

    watch the original complete announcement by He Jankui
  • Development of a new form of social inequality

    Our society already has several forms of inequality and there is a serious concern associated with gene editing and gene therapy for bringing a new form of inequality in our society.

    You see, Gene therapies and treatments like stem cell therapy are really expensive, and genetic tampering like this can be only afforded by rich people.

    This will give rise to a new kind of inequality in our society which would lead to all kinds of discriminations and conflicts

  • Religious Concerns

    Many religious groups argue that by trying to tamper with our genes – Are We “Playing God”?

    According to religious groups the genetic code we have is the essence of our life itself and has been written by God himself.

    Religion has been a strong backbone of our society and a huge part of the society does not understand the benefits of genetic research.

    The need is to find a unified approach to education which can help our society move forward together.

  • Consent for genetic alteration

    There is a reason why germline therapy is controversial,

    Even though the treatment can prevent future generations from a specific disease  it might also have an unexpected side effect

    The people who would be affected by these side effects are not born yet so they can’t choose whether to have the procedure done or not.

After all the reasons that have been mentioned what are views on the practice of gene editing and gene therapy.

Let me know in the comment section

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