in #steemstem6 years ago (edited)

In August 2017 United States Food and Drug Administration (USFDA) approved Yescarta (Axicabtagene ciloleucel) therapy to treat adults with certain types of large B-Cell lymphoma (a type of blood cancer). Yescarta uses chimeric antigen receptor (CAR) T-cell therapy for treatment.Last month of previous year FDA approved Luxturna, first in vivo gene therapy, for the management of blindness due to Leber'scongenital amaurosis.

Gendicine, first commercial gene therapy, was approved in China for the treatment of certain cancers. In 2011 Neovasculgen, registered in Russia as the first-in-class gene-therapy drug for treatment of systemic peripheral artery disease, including limb is chemical. In 2012 Glybera, became the first treatment to be approved for clinical use in either the United States and European Union after its endorsement by the European Commission.


What is Gene therapy

A technical manipulation which involves the replacement of defective genes with the normal ones in order to treat genetic disorders. It is an artificial method of introducing the DNA into the cells of human body. First time gene therapy was successfully accomplished in the year 1989, by the National Institutes of Health.
Successful therapeutic use of gene transfer and first direct insertion of human DNA into the nucleus was performed by French Anderson in a trial starting in September 1990.
Gene therapy is precision of the procedure and the intention of direct therapeutic effects.Medical procedures that introduce alterations to a patient's genetic makeup can't be always considered gene therapy.For example bone marrow transplant may lead to the change in genetic make up of the cell but is not intentional, we can't consider it gene therapy.


Gene therapy is classified into two types on the basis of type of cell, the cell on which the therapy is done.
  • Somatic gene therapy.

  • Germ line gene therapy.

In formar case the therapeutic genes are transferred into any cell other than a gamete or undifferentiated stem cell and in later case Germ line gene therapy (GGT), sperm or egg cells are modified by the introduction of functional genes into their genome. Thus modified germ cell causes all the organism's cells to contain modified genes.

Why we need gene therapy?

Gene therapy is considered future management of many diseases with worst case prognosis like cancer, viral infections and congenital diseases. Apart from these, potential scope of gene therapy is considered in infertility, gene doping and human genitic engineering. Experiment done on mice has shown that fertility can be restored by using the gene therapy method CRISPR. Gene doping though still hypothetical is a non-therapeutic use of gene therapy by athletes in order to improve their performance in sporting events. It has moral and ethical considerations. Germ line engineering of Human genitic engineering can increase the memory of a person, change its physical appearance, increase life span of an individual and augment the physical strength.Though the committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017 but only in stringent oversight in serious conditions.

Some Major challenges and unsolved problems!

Shelflife of Therapeutic genes

Before gene therapy can start acting a permanent cure for a condition, the DNA introduced into target cells must remain physiologically active and the cells containing DNA must be stable. Problems start encountering when integrating therapeutic DNA, genome and the rapidly dividing nature of many cells prevent it from achieving long-term treatment goals. So the patient may require multiple treatments plans.

Host body Immune response to foreign genes

Any time a foreign object or material is introduced into human body the immune system is activated to attack the invader. So it becomes obvious that immune system reduces gene therapy effectiveness, if not reject it. The immune system's increased response to viruses that it has seen before reduces the effectiveness and will lead to multiple treatments.

Problems with viral vectors

Vector is a medium that cause delivery of DNA into cells. Mostly used vectors are viruses. Viral vectors have the risks of toxicity, inflammatory responses, gene control and other issues like targeting.

Multigenic disorders

Many disorders are controlled by multiple genes, such as high blood pressure,heart disease, Alzheimer's disease and diabetes militus can be treated with single gene therapy which in turn complicates gene therapy and may need multiple therapies which is impossible and costly. In case of multiple therapies there are chances of breach in the Weismann barrier (barrier which separates somatic and germ-line) protecting the testes, patentially changing the germline, will lead ethical concerns of regulations in many countries that prohibit the said practice.

Insertional mutations to host

Place of integration of therapeutic DNA in the host cell in a sensitive spot in the genome can lead to the process of mutagenesis. For example if the integration happen in place of tumor suppressor gene, the therapy could induce a malignant tumor that can be more dangerous than the disease under treatment. The same has resulted in clinical trials for X-linked severe combined immunodeficiency (X-SCID) disease patients, where hematopoietic stem cells were transduced with a corrective transgene through a retrovirus, and this led to the development of T cell leukemia in 15 percent of patients under clinical trials.One possible solution to this is adding another functional tumor suppressor gene to the DNA to be integrated in host. This leads to another problem, longer the DNA, the harder it is to integrate into cell genomes. CRISPR technology allows researchers to make much more precise and short genome changes at exact locations.

Cost vs benifit ratio

In 2012-2013, Alipogene tiparvovec or Glybera, for example were available at a cost of $1.6 million per patient, was reported in to be the world's most expensive procedure or drug at that time.

Clinical trials and related eaths

The last and the most concerned challenge is deaths happened in clinical trials.At least, hree patients deaths have been reported in gene therapy clinical trials, getting the field trials under close scrutiny. The first one happen to be Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response. Another X-SCID patient died of leukemia in 2003. In 2007, a rheumatoid arthritis patient died from an infection; though the investigation concluded that the death was not related to gene therapy but because of other systemic disorder.


Both the images used in the article are free from copyrights

Hi, this article is written by Dr Muzaffar Hussain(@muzi0202) . If you like my blog and science related articles kindly resteem, upvote and follow me.


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