Enzyme Replacement Therapy Vs Gene Therapy

  • Batoul SalamahBachelor’s degree in Pharmacy from Damascus University\Syria
  • Helen McLachlanMSc Molecular Biology & Pathology of Viruses, Imperial College London

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When you hear the words gene therapy or enzyme therapy, you probably think that these are science things that you can’t understand, but these therapies have become more prevalent and useful in the therapeutic area than you might think, and they have given significant results.

What is enzyme replacement therapy vs. gene therapy?

  • These are therapy procedures that are used to treat some rare or inherited conditions that can’t be treated with typical or traditional therapies
  • Each of them is different to the other, but they both share the importance of being new and effective therapies

What are enzymes and genes?


  • Enzymes are proteins that play a critical and important role in the chemical reactions in our bodies
  • They are essential in many processes like digestion, breathing, muscle building, and nerve function


  • In order to understand genes, we need to understand chromosomes and DNA as well. These three substances work together to create the characteristics of the human being.
  • As we know, our bodies consist of trillions of cells, and each cell contains chromosomes that carry the DNA, which is responsible for building the human structure. Genes are segments of the DNA, and they are the building blocks of the body; they give instructions to make proteins and to do other things in the body to give it its unique characteristics.

What is enzyme replacement therapy (ERT)?

  • Enzyme replacement therapy1 is a treatment that is used to replace a missing enzyme in a patient who suffers from a congenital or inherited enzyme deficiency
  • The deficient enzyme is replaced through intravenous infusions with another one that comes from human or animal tissue. They may also be produced by recombinant techniques.

Examples of conditions treated with enzyme replacement therapy

The enzyme alpha-1-antitrypsin (A1AT) deficiency

This enzyme’s deficiency is associated with early-onset emphysema, which happens due to a lack of leukocyte elastase inhibitors, and, in turn, leads to progressive lung damage.

Gaucher disease

Gaucher disease is an inherited deficiency of the enzyme lysosomal acid β-glucocerebrosidase, which leads to the accumulation of lipids in the lysosomes of major tissues such as the liver, spleen, and bone. It causes anaemia, enlarged spleen and liver, bruising, fatigue, and other symptoms. 

The enzyme adenosine deaminase deficiency (ADA)

Adenosine deaminase deficiency is an inherited disorder that causes damage to the immune system and severe combined immunodeficiency, which might lead to a lack of immune protection from bacteria, viruses, and fungi.

Fabry disease

Fabry disease is an inherited neurological disorder that happens as a result of the enzyme alpha-galactosidase-A deficiency, which leads to the accumulation of lipids in the autonomic nervous system (which controls involuntary functions like breathing and heartbeat), in addition to other organs like the kidneys and eyes. 

Pompe disease

Pompe disease is a genetic disorder that happens due to the lack of an enzyme called acid alpha-glucosidase (GAA), which causes the accumulation of sugar glycogen in the cells, causing progressive muscle weakness, slow growth and respiratory infections, amongst other things.


This is group of inherited metabolic disorders that result from the absence or malfunctioning of specific enzymes that the body needs. 

Wolman disease

Wolman disease is a deficiency of the enzyme lysosomal acid lipase (LAL), which causes severe symptoms like enlarged liver and spleen, liver failure, diarrhoea, and vomiting in the neonatal or infantile period.

Enzyme replacement therapy risks

  • Local infusion reactions
  • Hypersensitivity, which can cause allergic symptoms (rash, fever, hypotension, angioneurotic oedema, bronchospasm, anaphylaxis, and cardio-pulmonary collapse), might lead to the inactivation of the enzyme
  • Minor, transient elevation in liver enzymes

Enzyme replacement therapy advantages

  • Recombinant and naturally purified enzymes are generally well tolerated, in addition to causing minimal systemic adverse reactions1
  • There are fewer side effects and wider availability than other treatments in some conditions
  • Results from clinical trials and the real-world setting confirm the efficacy and safety of ERT2

Enzyme replacement therapy disadvantages and limitations

  • ERT3 can trigger the immune response against it, which might reduce the therapeutic outcomes
  • ERT can’t cross the blood-brain barrier (BBB) and reach the central nervous system (CNS), which is considered a great challenge for it
  • There are sometimes restrictions on soluble enzymes
  • Low bioavailability due to a high biodegradation rate, which can affect the therapeutic results
  • ERT is not a cure, and it needs to be a recurrent and lifetime treatment because it only replaces the missing enzyme and doesn’t make the body reproduce it, and that leads to another problem, which is the high cost of this therapy

What is gene therapy?

  • As we said before, genes contain our DNA, which determines our characteristics, and each gene is responsible for a specific one
  • When there is a defect in a gene, this leads to a disorder in the body; therefore, gene therapy aims to repair this flaw in the defective gene, using genetic material, in order to treat the condition it has caused

Gene therapy works through different mechanisms

  • Through replacing the defective gene with another healthy one
  • Inactivating the disease-causing gene
  • Introducing new genes to the body to treat the condition

The delivery of the genetic material

There are two main methods of delivery:

  • In vivo: The gene is delivered directly to the body through injections
  • Ex vivo: The cells are removed from the body, and the gene is delivered to them outside; then they will be returned to the body

There are various types of therapy products

  • Viral vectors: Since viruses have a natural ability to enter cells and deliver genetic materials, they are used as vectors (carriers) for the therapeutic gene after removing their ability to cause diseases in the body
  • Bacterial vectors: Some bacteria can be modified to work as vectors as well
  • Plasmid DNA: DNA molecules are engineered genetically to carry healthy genes to the cells
  • Human gene editing technology: In this procedure, technicians disrupt harmful genes or repair the mutated ones

Diseases treatable with gene therapy

Most of these gene therapies4 are still in clinical trials after having approved protocols to treat the following disorders:

  • Adenosine deaminase deficiency (ADA)
  • α-1 antitrypsin deficiency (a condition that raises the possibility for lung diseases)
  • AIDS
  • Some cancers
  • Cystic fibrosis
  • Familial hypercholesterolemia
  • Fanconi anaemia
  • Gaucher disease
  • Haemophilia B (a rare genetic bleeding disorder)
  • Rheumatoid arthritis

Approved gene therapies

  • Certain inherited eye diseases and spinal muscular atrophy in children younger than 2 years old
  • Certain blood cancers, such as acute lymphoblastic leukaemia and diffuse large B-cell lymphoma

Gene therapy risks

  • Possibility of some cancers
  • Allergic reactions
  • It can cause damage to an organ or tissue

Gene therapy advantages

  • Hopeful treatments for patients who suffer from these debilitating disorders
  • It is a cure, not just a replacement therapy

Gene therapy disadvantages

  • The treatment is not guaranteed and might not reach the targeted cells.
  • The process is complicated, and the long-term effects are unknown.

Enzyme replacement therapy vs. gene therapy

It’s not accurate to compare these two therapies because they are different and each one has its own features and attributes:

  • Enzyme replacement therapy is administered directly through intravenous infusions, while gene therapy is given with special vectors.
  • Enzyme replacement therapy isn’t a cure, and the patient must take it continuously, while gene therapy is a complete cure.
  • The efficacy of enzyme replacement therapies is confirmed, while most gene therapies are still in clinical trials.
  • The side effects of enzyme replacement therapy are considered mild compared to the gene therapy risks.


Which enzyme is used in replacement therapy?

There is not a specific enzyme that is used in all enzyme replacement therapies; each condition has a specific enzyme.

How does enzyme replacement therapy work?

The replacement enzyme is given through intravenous infusions; after that, they do their job as if they were normally secreted within the body.

What cells are used in gene therapy?

Stem cells are the cells used in gene therapy, and they provide two major benefits: Firstly, this type of cell is self-renewing and is able to survive for the lifetime of the patient. Secondly, stem cells provide daughter cells that are matured into specific specialised cells in each tissue.

What is the main goal of gene therapy?

Its essential goal is to treat inherited, incurable diseases that may be life-threatening and cause patients to suffer throughout their lives.


Each one of these therapies has its own approach and object, yet they both aim to help patients end their suffering, or at least help them cope with their conditions. Although a lot of therapies are still in clinical trials, the results are promising.


  1. Enzyme replacement therapy. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548796/
  2. Concolino D, Deodato F, Parini R. Enzyme replacement therapy: efficacy and limitations. Italian Journal of Pediatrics [Internet]. 2018 Nov 16 [cited 2024 Jan 11];44(2):120. Available from: https://doi.org/10.1186/s13052-018-0562-1
  3. Enzyme replacement therapy: current challenges and drug delivery prospects via extracellular vesicles. Rare Disease and Orphan Drugs Journal [Internet]. 2022 Jul 4 [cited 2024 Jan 11];1(3):null-null. Available from: https://www.oaepublish.com/articles/rdodj.2022.09
  4. Gonçalves GAR, Paiva R de MA. Gene therapy: advances, challenges and perspectives. Einstein (Sao Paulo) [Internet]. 2017 [cited 2024 Jan 11];15(3):369–75. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823056/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Batoul Salamah

Bachelor’s degree in Pharmacy from Damascus University\Syria
Associate’s degree in Health Sciences from the University Of the People\United States

Batoul has significant expertise in various domains of pharmacy. For instance, she worked in several community pharmacies, where she worked directly with patients. She worked as a senior pharmaceutical representative as well, where she worked directly with doctors and physicians. And currently, she’s working as a freelance medical writer, where she puts her humble expertise into helping people get the correct information about their health and how to take care of it.

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