Gene therapy in children | Types, methods and uses

Related theory questions

  1. Gene therapy in children (2006/1) 10
  2. Gene therapy (2007/1) 5
  3. Primary and secondary prevention of genetic disorders 5+5 (1/2016)

What is gene therapy?

Gene therapy involves correcting or replacing a defective or absent gene, to modify, cure or prevent a genetic disease

This includes treatment of a disease/ disorder, especially one caused by the inheritance of a defective gene, by replacing them with healthy ones using a vector for transfer.

Types of gene therapy

  1. Somatic
  2. Germ line

Somatic gene therapy

  1. Good gene is transferred into targeted cells to treat the patient — but not the patient's future children.
  2. Genes do not get passed on to offspring.
  3. The chance that the disease will be passed on to the offspring do not reduce.

Germ line gene therapy

  1. Genetically modified/engineered egg or sperm cells are used for fertilization, which then passes new genetic changes to future generations.
  2. Potential for preventing inherited disease.
  3. Little researched so far.
  4. Technicaly chalanging
  5. Ethical challenges

Methods of gene therapy

Methods for genetic manipulation used in gene therapy are

Gene transfer or gene addition

  1. A new gene is introduced into cells to help fight a disease.
  2. Introduce a non-faulty copy of a gene to fight the altered copy, causing disease.

Genome editing

Instead of introducing new genetic material into cells, genome editing introduces molecular tools to change the existing DNA in the cell.

CRISPR-Cas9 is an example. It is the simplest and most precise method of genetic manipulation.

Genome editing works via the following mechanism

  1. Fix a genetic alteration underlying a disorder, so the gene can function properly.
  2. Turn on a gene to help fight a disease.
  3. Turn off a gene that is functioning improperly.
  4. Remove a piece of DNA that is impairing gene function and causing disease.

Ex vivo vs In vivo gene therapy

Ex vivo gene therapy

Cells removed from the body are altered by introducing DNA using a viral vector. The altered cells are injected back usually by an intravenous (IV) infusion.

In vivo gene therapy

In this, new genetic material is created in a lab and delivered to the patient via vector which carries the new genetic code/information. The vector is injected in the blood, or directly in the target organ.

Vector used for gene transfer


  1. Viruses can enter cells and deliver new genetic material into the nucleus of target cells
  2. More efficient than non-viral gene transfer
  3. Human viral pathogens are turned nonpathogenic for use
  4. They can infect and deliver encoded transgenes to a wide spectrum of cells and/or tissues.
  5. Safety issues

The most commonly used viral vectors are

  1. Adenovirus
  2. Herpes simplex virus type 1
  3. Retrovirus/lentivirus

Non-viral vectors

  1. DNA is used to transfect organs like skeletal muscle.
  2. Systemic administration is not possible due to the clearance of DNA by serum nucleases.
  3. Apart from intracellular and extracellular barriers, a number of other challenges also need to be overcome in order to increase the effectiveness of non-viral gene transfer.

Pediatric diseases with potential for gene therapy

At present, the utility of gene therapy is limited to research trials and very few are approved

Gene therapy targeting hematopoietic stem cells

  1. x linked scid
  2. ADA deficiency
  3. Wiskott - Aldrich syndrome
  4. Chronic granulomatous disease
  5. Fanconi anemia
  6. childhood cerebral adrenoleukodystrophy
  7. Metachromatic leukodystrophies
  8. x linked lymphoproliferative syndrome

Gene therapy for the treatment of malignancies

Majority of research is focused on this.

Pediatric cancer therapy with gene-modified t cells

  1. EBV associated post-transplant lymphoproliferative disorder
  2. EBV-positive Hodgkin disease
  3. EBV-positive nasopharyngeal carcinoma
  4. Chimeric t cells for tumor therapy


  1. Melanoma
  2. Osteosarcoma
  3. Neuroblastoma

Metabolic diseases

  1. Lipoprotein lipase protein deficiency
  2. Adrenoleukodystrophy
  3. Metachromatic leukodystrophy
  4. Mucopolysaccharidoses
  5. Canavans disease
  6. Focal neocortical epilepsy
Want to read approach to IEM's?


  1. ß-thalassemia
  2. scd
Want to read Iron chelation therapy?

Gene therapy for skin disorders

  1. Netherton syndrome
  2. epidermolysis bullosa

Childhood blindness

  1. Leber congenital amaurosis(rpe65)
  2. Achromatopsia 1
  3. x-linked retinitis pigmentosa(prph2 gene)

Respiratory disorders

Cystic Fibrosis

The process of the direct delivery of the cystic fibrosis transmembrane regulator (CFTR) gene into respiratory tract epithelium cells as the target tissue is followed.


  • Duchenne muscular dystrophy

Other uses

  1. Corneal and retinal repair
  2. Pancreatic islet cell therapy

FDA approved gene therapy in children

Zolgensma is FDA approved for spinal mascular atrophy type-1.

What are the hurdles in gene therapy?

  1. Short-lived nature of therapy as against long term expectations
  2. Adverse immune response including cytokine storm
  3. Viral vectors-toxicity &inflammatory responses
  4. Multigene disorders are difficult to manage
  5. Breach of Weismann barrier between somatic and germline cells. Weisman said that which protecting testis- potentially modifying germline
  6. insertional mutagenesis

What is Weisman's Barrier?

Weismann barrier was proposed by Weisman between somatic and germline cells. Hereditary information moves only from germline to body cells and not vice-versa. This protects the potential modification germline.

With gene therapy now this concept is challenged since it is possible to reprogramme somatic cells into pluripotent cells.

Regulation of gene therapy in India by ICMR

In India, ICMR releases clinical trials guidelines for gene therapy.

In case you want to dig deep into guidance on gene therapy products, here is the link

All gene therapies are considered research therapies. Somatic cell gene therapy is permissible for the purpose of preventing or treating a serious disease when it is the only therapeutic option. Germline therapy is prohibited under the present state of knowledge.
Children could be candidates for therapy if the therapy is meant for childhood disorders.

Journey of gene therapy

The journey of gene therapy has witnessed dramatic ups and downs in the field, Gene therapy is promising but very slow to develop.

There are several gene therapies approved in western countries and extensive trials are on the way.

Several dedicated academic portals are constantly trying to disseminate the information.

Gene therapy has also attracted the interest of pharmaceutical industries which are trying to bring gene therapy upfront. While the stakes and risks in gene therapy are quite high, the outcomes can change the entire face of medicine.


about authors

Avinash T | DCH DNB (Pediatrics), Dip Child right laws

Avinash has completed DNB in Pediatrics after DCH, from CSI hospital, Bengaluru with further training in child rights law

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