Gene Therapy - The potential hope for incurable diseases in future.
Hello friends, hope you are all fine . I have closed series on pulmonary medicine in which I have covered only three topics namely ASTHMA , COPD AND PNEUMOTHORAX . Now I have decided to make an article on the much talked and much heard topic which is GENE THERAPY. Before jumping on to the topic, I think basic albeit brief introduction of cell , DNA , chromosome and gene is mandatory. . So let us begin
Human body is organized aggregation of about more than 10 billion cells. It means cells are the building blocks of life. So to understand the life , we have to first understand the composition of individual human cell. As we all know that,cell is the basic structural , functional and biological unit of life
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Author: Mediran
We also know that cell is not a single structure . Cell by itself is an aggregation of small organelles , each of which has discrete role to play , to maintain the functionality and integrity of cell as a whole. To describe each organelle of cell, is neither need nor scope of my current topic . So I will only be discussing here the relevant part of cell structure .Cell is a plasma membrane bound unit which encloses a fluid filled space known as cytoplasm which contains cellular organelles (endoplasmic reticulum , lysosomes , peroxisomes , mitochondria etc ) surrounding nucleus . Nucleus is just like a headquarter which commands cell to perform desired functions . The chief of this headquarter which sends the above mentioned commands is deoxyribonucleic acid (DNA).
What is DNA?
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Author Zephyris
DNA is double helical aggregation of nucleotides and each nucleotide in turn is formed by three units, one each of nucleobase (Adenine, guanine , cytosine and thymine ) , deoxyribose sugar and a phosphate group . To be more specific , it is the arrangement of nucleotides within the DNA molecule that determines the nature of genetic information . This arrangement of nucleotides within a particular region forms genes
Take a break here to recapitulate, what determines genetic information in a human. You must be able to answer this question this way, In a cell, it is the nucleus which stores genetic information and within the nucleus it is the DNA and within the DNA , it is the arrangement of nucleotides within its helices known as genes which actually determines the genetic information to be given to rest of the functionalities of cell for survival of human being as a whole.
DNA is not haphazardly present within the nucleus but is present in the form of scissor ( X shaped) like structures called Chromosomes. The logic behind this arrangement is simple to understand . It is to simplify the distribution of DNA between daughter cells during cell division and during protein synthesis . Before cell division , the scissor like structure separates at the joint ( centromere) and each blade of scissor duplicates to form a complete set to be transferred to daughter cell. Similarly , during protein synthesis codons of gene are code into mRNA (messenger RNA) which is than decoded in ribosomes to form a desired protein . Formation of protein is one of the means of gene expression . Proteins so formed have many uses like structural components of our organs , catalyse various enzymatic reactions in different metabolic pathways of body .
GENE THERAPY (AKA GENE TRANSFER)
Oxford dictionary defines therapy as "treatment intended to relieve or heal a disorder". Extrapolating the same definition to gene therapy, we can define or try to understand it as "treatment with the help of genes to correct defective genes". Gene therapy is a potential therapy in genetic disorders of diverse etiologies ranging from monogenic disorders (single gene defect like cystic fibrosis ) to complex disorders involving cardiovascular system , nervous system and even cancer.
Which cells are targets for gene transfer ?
Target cells for gene transfer can be our germ cells ( sperm and ova) or somatic cells ( non germ cells).Former is called germline gene therapy (GGT) and later is called somatic cell gene therapy(SCGT).
In GGT the foreign gene is introduced into the nucleus of germ cells and therefore , the resulting modified genome is heritable to future generations. As a result the organism resulting from combination of modified gametes will have foreign genes in all the cells of body. So this procedure has limited scope due to ethical concern .
In SCGT, genetic modification of cells other than germ cells is carried out. So this type of genetic modification is not heritable but is limited to the individual in which it is carried out. SCGT can be carried ex-vivo or in-vivo. In Ex-Vivo approach the cells are modified outside the body and than introduced into the body. In In-vivo approach cells are not taken out of body but are modified inside body. SCGT is the main focus of modern researchers in field of medical science to treat diseases. So by gene therapy we actually mean SCGT.
What functions does the transferred gene carry out in target cells?
Depending upon the condition for which gene therapy is indicated , the transferred gene can be introduced with the aim -
To replace the defective gene causing disease.
To substitute the non functional gene.
To alter the regulation of abnormal gene.
One point to be clarified here is that gene therapy is not only for genetic disorders but it has significant role in non genetic disorders and cancers as well.
How to deliver therapeutic gene into target cell?
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Gene delivery into target cell is not like an oral or parenteral medication which is picked up by target cells from the blood and used for desired purpose. But gene delivery requires specific vehicles for transport to the destination .These vehicles used for gene delivery are called vectors .Two types of vectors are used - viral vectors and non viral vectors .
Viral vectors include viruses like retroviruses , adenoviruses, adeno like virus, lentoviruses etc. The target gene is incorporated into the virus and the virus is introduced into the target cell. Viruses than introduce the therapeutic genes into the host's genome and triggers it to replicate and express the effect of therapeutic gene. However, viral vectors have certain shortcomings like body may mount an immune response against the virus and neutralize its anticipated purpose or may even result in viral infection . Also immune overt reactions can result in serious effects like autoimmune diseases and even death . Moreover, viral vectors like adenovirus have short term expression and limited transduction of cells which necessitates repeat therapy and thus financially cripple the recipient .
Non-viral vehicles for therapeutic gene delivery may include use of liposomes , plasmids and direct inoculation of naked DNA into target cell . Non viral vectors make use of modern technology for creating pores into the target cell and than firing genes with the help of gene guns . Modern technology that has been put in use include ultrasound waves and the procedure is known as sonoporation , or magnetic field like MRI and the procedure is known as magnetofection . As I mentioned non viral vectors are technologically advanced but are not free of limitations .It has been found that these vectors have low therapeutic efficacy .
What stops gene therapy from creating miracles ?
I think by now it must be clear to you that gene therapy is not as easy as other modalities of treatment like medication , surgery or radiotherapy etc . Limitations like ethical concern , technical complexity , viral and non viral vector associated limitations , immune response against gene introduced , repeat therapy are not the only hurdles but the worst thing is that gene therapy can even induce tumor in recipients body and may even cause DEATH. It has been seen that 15% of patients subjected to gene therapy have developed T-cell tumor .
Is there any use of gene therapy for healthy individuals ?
Yes there is scope of gene therapy in the field of sports to increase athletic performance and endurance . Such use of gene therapy is non therapeutic and is known as gene doping. However , gene doping has met no uniform consensus. It is subject of fiery debate whether gene doping should be legalized or not .
Where there is hope ; there is life .
Bitter truth about gene therapy is that , it has not been legalized for clinical use yet. it is still used for research purposes. But there is potential hope associated with it . About 1800 clinical trials linked with gene therapy for various diseases have been conducted . Researches which are being carried for whatever disease have shown positive results. Let me share results of one research carried for cystic fibrosis which is still going on. Of its four phases 2 phases have been completed and the results showed that repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis : a randomised, double-blind, placebo-controlled, phase 2b trial has shown significant albeit modest increase in FEV1 (FORCED EXPIRATORY VOLUME IN ONE SECOND) in patients who were nebulised CFTR gene pGM169/GL67A gene–liposome over 12 months period than placebo.
REFERENCES
https://en.m.wikipedia.org/wiki/Cell_(biology)
https://ghr.nlm.nih.gov/primer/basics/cell
https://en.m.wikipedia.org/wiki/Chromosome
https://ghr.nlm.nih.gov/primer/therapy/genetherapy
https://googleweblight.com/i?u=https://www.sciencedaily.com/terms/gene_therapy.htm&hl=en-IN
https://en.m.wikipedia.org/wiki/Gene_therapy
https://www.nature.com/scitable/topicpage/sports-gene-doping-and-wada-764
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