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Medha Shinde
Apr 144 min read

An Introduction to Gene Therapy

Gene therapy involves using genes to treat, prevent, or cure a medical condition. It frequently involves introducing new copies of a damaged gene or substituting a healthy copy of a gene absent or faulty in a patient's cells. Gene therapy is used to treat acquired disorders such as leukemia or inherited genetic diseases like hemophilia and sickle cell disease.


Gene therapy involves using Nucleic acids (DNA or RNA) to treat, cure, or prevent human diseases. Depending on the disease type, this can be accomplished by either lowering the levels of a harmful defective gene product using sophisticated tools like naked oligonucleotides and viral and non-viral vectors or delivering a functional, therapeutic gene to replace the faulty or missing endogenous counterpart.


In vivo and ex vivo gene therapy


Figure 1: Genetic material can be delivered to target cells inside a person’s body, called in vivo gene therapy.



Figure 2: Genetic material can be delivered to a person’s cells after they are removed from their body; this is called ex vivo gene therapy.


The best way to introduce genetic material into a cell is determined by the condition, the cells involved, and the treatment's ultimate objective. For instance, an in vivo therapy that specifically targets cells, such as those in the eye, effectively treats conditions that impact an individual's ability to see or use their eyes. When treating blood-related disorders like hemophilia, where a person's self-renewing stem cells can be genetically modified to produce a viable working gene and subsequently injected into their body, an ex vivo treatment may be a better option.


Figure 3: In vivo and ex vivo delivery.


"In vivo gene therapy" describes the direct administration of genetic material to a particular organ, such as the eye, either locally or intravenously (via an IV). In vivo gene therapy employs a vector to directly introduce functional copies of a gene into target cells to treat a defective or absent gene. Gene therapy delivered in vivo has been demonstrated in numerous scientific domains. Genes are delivered in vivo by a few licensed gene treatments. Targeted in vivo gene therapy will develop further as scientists work to improve gene delivery techniques.


Ex vivo gene therapy removes particular cells from an individual, changes their genetic makeup in a lab, and reintroduces the altered cells into the original host. Ex vivo gene therapy replaces target cells with a defective or absent gene by genetically modifying the patient's stem cells. These days, hematopoietic stem cells (HSCs) are the most common subject of ex vivo gene therapy; this is utilized to treat diseases of the blood and immune system and genetic disorders affecting tissues and organs accessible to blood cells.


Gene delivery method


Gene therapy inserts genetic material into the cell's nucleus, such as a transgene or nuclease. A vector is the term for the device that carries genetic material. Consider a vector as a delivery vehicle that delivers items (genetic material) to designated destinations (target cells).

  1. Viral Vectors—Viral vectors are built using a virus's blueprint—not the actual virus itself. Scientists use only the portions of the virus's blueprint that aid in the delivery of genetic material. At the moment, viruses are the most popular carrier for FDA-approved gene treatments. The three most common viral vectors used in gene therapy are: 

  • Lentiviral vectors (LVVs): LVVs are a species of retrovirus. HIV, the most well-studied lentivirus, is used to design gene therapy vectors. These vectors can insert genetic material into dividing and non-dividing cells, enhancing durability and allowing continued gene expression.

  • Adenoviral vectors (AdVs):The adenovirus, the first viral vector in gene therapy, has shown promise in cancer treatment, although some may trigger dangerous immune reactions, despite ongoing research.

  • Adeno-associated viral vectors (AAVs):Adenoviruses, discovered in the 1960s, are the standard viral vector used in gene therapy. Various types target various cells, including kidney and brain cells, and are currently involved in clinical trials.


  1. Non-viral vectors- Non-viral vectors transfer genetic material into a cell physically or chemically. This can be accomplished by chemical means (developed in a lab) or physical means (like a needle penetrating a cell). The non-viral vectors that are being studied the most include polymer-based vectors, chemical disruption, and electroporation. The effectiveness and safety of non-viral methods are currently being researched. Some examples of non-viral vectors in gene therapy are: 

  • Physical vector - Electroporation: Electroporation—a non-viral delivery technique—is being investigated for gene therapy delivery in clinical trials. Scientists create transient holes in a cell membrane through electroporation by applying electrical pulses. Gene therapy can be injected into these pores and administered to the cell where it is most effective. Recent clinical trials have utilized electroporation for gene therapy on patient cells outside the body despite its initial exploration in vivo.

  • Chemical vector: lipid nanoparticle:Lipid nanoparticles (LNPs) are the most used non-viral delivery technique. LNPs encapsulate genetic material to transfer it to target cells. Genetic material breaks down quickly without a delivery mechanism like an LNP, making it unable to enter target cells. LNPs give researchers a means of delivering and safeguarding genetic material for in vivo gene therapy. LNPs have a wide range of possible applications in gene therapy since they are easy to make, effective, and scalable to the size of the material being supplied.



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