Gene therapy is a medical approach that aims to treat or prevent diseases by modifying a person's genes. The basic idea behind gene therapy is to introduce new genetic material into a patient's cells to replace faulty or missing genes or to enhance the body's ability to fight off diseases. This field holds tremendous promise for treating genetic disorders and other conditions that have a genetic component.

1. Dr. Trilok Mandal (BVSc & AH)
Department of Animal Breeding and Genetics (MSc)
Agriculture and Forestry University (AFU) Rampur, Chitwan, Nepal
Email: trilokmandal97@gmail.com
What is gene therapy? How gene therapy is useful for treatment of genetic disease.
Gene therapy is a medical approach that aims to treat or prevent diseases by modifying a
person's genes. The basic idea behind gene therapy is to introduce new genetic material into a
patient's cells to replace faulty or missing genes or to enhance the body's ability to fight off
diseases. This field holds tremendous promise for treating genetic disorders and other
conditions that have a genetic component.
There are different types of gene therapy techniques, but the two main categories are:
1. Somatic Gene Therapy: This type of gene therapy targets the somatic cells, which are
non-reproductive cells of the body. The genetic modifications made through somatic
gene therapy are not passed on to future generations, as they do not affect the germline
(reproductive cells like sperm and eggs). Somatic gene therapy is mainly used to treat
specific diseases in individual patients.
2. Germline Gene Therapy: In contrast to somatic gene therapy, germline gene therapy
involves modifying the genetic material in reproductive cells (sperm or eggs) or
embryos. This alteration affects not only the individual but also future generations.
Germline gene therapy raises significant ethical concerns and is currently a topic of
much debate due to the potential for unintended consequences and ethical
considerations related to human genetic manipulation.

2. Figure 8.5 A brief outline of gene therapy strategies. A direct deliv-ery strategy is based
on constructing a virus- based vector to deliver the therapeutic gene (either as an extra
functional copy integrated randomly to the genome, or to replace one of the defective
genomic copies using homologous recombination) (left panel). This vector will be
packaged into pseudoviral particles and delivered directly to the patient, commonly
through injections (1). Cell- based delivery strategies are in general based on delivery
of the therapeutic gene to cells outside the patient’s body, and then delivery of these
geneti-cally modif i ed cells back to the patient (right panel). There are several
approaches, only some of which are summarized here. Embryonic stem (ES) cells (e.g.,
obtained from cell banks) are modif i ed using gene therapy vectors (2), and are either
transferred to the patient as genetically modif i ed ES cells, expected to home in and
differentiate into the desired cell type in situ (2a), or are differentiated into the desired
cell type in vitro and delivered to the patient thereafter (2b).
Alternatively, patient- derived adult stem (AS) cells may or may not be directly
obtained from the patient, may be used for genetic modif i -cation by gene therapy
vectors (3), and are delivered directly to the patient as genetically modif i ed AS cells
(3a), or are differentiated into the desired cell type in vitro and delivered to the patient
thereafter (3b). Yet another approach preferred by some scientists is to use the patient’s
own somatic cells to generate iPS cells (4), and then proceed as in ES or AS cells (4a
and 4b). One other alternative studied by some researchers is to directly
transdifferentiate somatic cells into the desired cell type while “correcting” the genetic
defect (5).
The process of gene therapy typically involves the following steps:
1. Identifying the faulty gene: First, scientists identify the gene responsible for the disease
or condition they want to treat.
2. Introducing the correct gene: The next step is to introduce a healthy copy of the gene
into the patient's cells. This is often done using viruses that have been modified to carry
the correct genetic material. These modified viruses act as delivery vehicles, delivering
the functional gene to the target cells.
3. Cell modification: The modified viruses are then introduced into the patient's body,
where they infect the target cells and insert the correct gene into the cell's DNA.
4. Expression of the new gene: Once the correct gene is integrated into the cell's DNA,
the cell can start producing the missing or functional protein, which helps in treating
the disease or condition.
Gene therapy offers a promising approach for the treatment of genetic diseases by addressing
the root cause of the condition at the genetic level. Unlike traditional treatments that may only
manage symptoms, gene therapy aims to correct or replace the faulty genes responsible for the
disease. Here's how gene therapy is useful in treating genetic diseases:
1. Correcting faulty genes: In genetic diseases, specific genes may be mutated or
dysfunctional, leading to the disease phenotype. Gene therapy can introduce a
functional copy of the gene into the patient's cells, effectively replacing the faulty gene

3. with a healthy one. This allows the cells to produce the necessary functional protein,
which helps in treating the disease.
2. Providing missing genes: Some genetic diseases occur due to the absence of a particular
gene, leading to the lack of a critical protein. Gene therapy can deliver the missing gene
to the affected cells, enabling them to produce the required protein and restore normal
cellular functions.
3. Temporarily silencing or editing genes: Gene therapy can also involve techniques like
RNA interference (RNAi) or gene editing (e.g., CRISPR-Cas9) to target and silence or
edit specific genes. In cases where an overactive or harmful gene is causing the disease,
these techniques can help reduce the gene's impact or correct its function.
4. Targeting specific cells: Gene therapy can be designed to target specific cell types
affected by the genetic disease. By delivering therapeutic genes directly to the affected
cells, the treatment can be more precise and minimize potential side effects on healthy
cells.
5. Somatic gene therapy: In many genetic diseases, somatic gene therapy is used, which
means only non-reproductive cells are targeted. This approach ensures that the genetic
modifications are not passed on to future generations, making it ethically less complex.
6. Potential for lifelong effects: Successful gene therapy can result in long-lasting effects,
potentially providing a lifetime of treatment benefits with a single intervention.
Gene therapy in animal diseases has shown significant promise in preclinical studies and
research, particularly in small animal models. Here are some examples of gene therapy
approaches that have been investigated for the treatment of animal diseases:
1. Canine Muscular Dystrophy: Canine muscular dystrophy is a genetic disorder that
affects dogs, particularly certain breeds like Golden Retrievers and Labrador
Retrievers. Researchers have used gene therapy to deliver functional copies of the
dystrophin gene, which is defective in muscular dystrophy, to the affected dogs. This
approach has shown to improve muscle function and prolong survival in canine models
of the disease.
2. Feline Immunodeficiency Virus (FIV): FIV is a lentivirus that affects domestic cats,
similar to HIV in humans. Gene therapy has been explored to develop FIV-resistant
cats by introducing genes that can inhibit viral replication and enhance the cats' immune
response.
3. Canine Leishmaniasis: Leishmaniasis is a parasitic disease that affects both humans and
animals. In dogs, the disease can be severe and difficult to treat. Gene therapy studies
have investigated the delivery of genes that can enhance the dog's immune response
against the parasite, potentially providing a more effective treatment option.
4. Canine X-linked Retinitis Pigmentosa: This inherited retinal disease causes progressive
vision loss in dogs. Gene therapy approaches have targeted the retinal cells to deliver
functional copies of the mutated gene, leading to improved vision and retinal function
in preclinical studies.

4. 5. Equine Joint Diseases: Horses commonly suffer from joint-related issues, such as
osteoarthritis. Gene therapy has been studied to introduce genes that promote cartilage
repair and reduce inflammation in affected joints.
6. Avian Influenza: Chickens and other birds are susceptible to avian influenza, a highly
contagious viral disease. Gene therapy has been explored as a potential method to
develop genetically modified chickens with increased resistance to the virus.
7. Severe combined immunodeficiency (SCID): Gene therapy has been successful in
treating some forms of SCID, often referred to as "bubble boy disease," by restoring
immune function.
8. Hemophilia: Clinical trials have demonstrated improved blood clotting in patients with
hemophilia by introducing the missing clotting factor genes.
9. Leber congenital amaurosis (LCA): Gene therapy has shown to improve vision in some
patients with LCA, a rare inherited form of blindness.
10. One notable example of successful gene therapy in animals is the treatment of canine
congenital blindness caused by a mutation in the RPE65 gene. This condition is similar
to Leber congenital amaurosis (LCA) in humans, which is a group of inherited retinal
disorders that cause severe vision loss or blindness at an early age.
11. Porcine Reproductive and Respiratory Syndrome (PRRS), a viral disease that affects
pigs and causes significant economic losses in the swine industry worldwide.
Researchers have been exploring gene editing techniques, such as CRISPR-Cas9, to
develop PRRS-resistant pigs. In one study, scientists used CRISPR-Cas9 to modify a
gene in pigs that provided resistance to the PRRS virus, and the pigs were found to be
less susceptible to the disease.
It's important to note that while gene therapy in animal diseases has shown promising results
in preclinical studies, translation to clinical applications can be complex and requires careful
evaluation. The safety, efficacy, and ethical considerations must be thoroughly assessed before
gene therapy can be considered as a viable treatment option for animal diseases on a larger
scale. Additionally, regulatory approvals and commercial adoption may take time before these
gene therapies become widely available in veterinary medicine. As research continues to
progress, gene therapy is likely to play an increasingly important role in improving the health
and well-being of animals affected by genetic diseases.