Gene Therapy Pros And Cons

Gene Therapy

Gene therapy Definition: Gene therapy is the insertion of genes into an individual’s cells and tissues to treat a disease, such as a hereditary disease in which a deleterious mutant allele is replaced with a functional one.

To be effective, the gene therapy requires methods that ensure the safe, efficient and stable introduction of genes into human cells.

Gene therapy uses genes to treat or prevent disease. First done on September 14, 1990 for Ashanthi DeSilva suffering from SCID where the missing gene introduced through processed WBC.

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Approaches for Correcting Faulty Genes

• A normal gene may be inserted into a nonspecific location to replace a nonfunctional gene.
• An abnormal gene could be swapped through homologous recombination.
  Repair through selective reverse mutation.
• The regulation of a particular gene could be altered.

Types of Gene Therapy

The cells in the body can be divided into two main categories: (1) somatic cells and (2) germ cells.

Somatic cell therapy: It involves delivering a correcting gene to somatic cells in the affected tissues.

Somatic cells are the nonreproductive cells and its therapeutic effect ends with the individual receiving it and is not passed on to the future generations.

Hence, somatic cell therapy is considered as a safer approach. This type of gene therapy is used for disorders such as cystic fibrosis, muscular dystrophy, cancers, and certain infectious diseases.

Germ cell therapy: In germ cell therapy, germ cells (egg or sperms) are used and it results in permanent changes that are passed on to the future generations.

Thus, it offers the possibility of permanently eliminating some diseases from a particular family and ultimately from the population. It is not accepted at present due to ethical reasons.

Arguments for Germline Gene Therapy

• Medical utility: The potential of a true “cure”.
• Medical necessity: May be only way to cure some diseases.
• Prophylactic efficacy: Better to prevent a disease rather than to treat pathology.
• Parental autonomy: Parents can make choices about what is best for their children.
• Easier, more effective than somatic gene therapy.
• Eradication of disease in future generations.
• Part of being human: Supporting human improvement.

Forms of Gene Therapy

There are two basic forms of somatic gene therapy: (1) ex vivo and (2) in vivo.

1. Ex vivo: Transfer of gene in cultured cells and finally these cultured cells are reintroduced into patients.

2. In vivo: Delivery of genes into cells of particular tissues. The gene may be transferred by a viral vector or by a nonviral method. This is most often used technique.

Vectors in Gene Therapy

The most common form of gene therapy involves insertion of normal gene into the genome with the help of certain carriers called vectors.

These vectors can be divided into two main types: (1) viral and (2) nonviral vectors.

Viral vectors: The various viruses include retroviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses.

Nonviral methods: Gene delivery can also be carried by nonviral methods.

These have some advantages. They do not elicit an immune response, safer and simpler to use and allow large-scale production.

The nonviral methods include: direct inoculation/naked DNA, liposomal-mediated DNA transfer, gene gun method, and dendrimers.

Pure DNA constructs and lipoplexes are used for in vivo transfer while bone marrow cells are used for ex vivo transfer.

Problems/Limitations of Gene Therapy

• Short-lived nature of gene therapy. Hence, patients will have to undergo multiple rounds of gene therapy.
• Immunotoxicity: Gene therapy may stimulate the immune response against introduced gene and reduce the effectiveness of gene therapy.
• Problems with viral vectors: Viral vectors may sometimes cause potential problems to the patient like: toxicity and inflammatory responses. In addition, the viral vector, once inside the patient, may recover its ability to cause disease.
• Gene silencing—repression of promoter
• Multifactorial disorders: Genetic disorders due to single gene mutations usually show best response to gene therapy. Unfortunately, some the most commonly occurring disorders (e.g., atherosclerosis, hypertension, diabetes, Alzheimer’s disease, and rheumatoid arthritis) are multifactorial and are difficult to treat effectively using gene therapy.
• Phenotoxicity—complications arising from overexpression or ectopic expression of the transgene.
• Risk of inducing a tumor (insertional mutagenesis): If the gene is integrated in the wrong place in the genome (e.g., in a tumor suppressor gene), it could induce a tumor.
• Risk of death: Deaths have occurred due to gene therapy.

Therapeutic Applications

• Not been approved for clinical use.
• Trials are being conducted on using gene therapy in the treatment of various genetic disorders, cancers, infectious diseases, and other diseases such as Alzheimer’s disease and atherosclerosis.