Genetic Healing: The Promise of Gene Therapy in Healthcare

 

        DNA, the genetic inheritance is either a boon or a curse. Researchers came up with Genetic advances that enabled us to render the DNA sequences  and paved a new pathway for the drug industry. Gene therapy is the modification of the genetic expression of a person by correcting the genetic alterations like mutations or modifications of site specific targets for therapeutic drugs. It is widely used in Europe, the United States, and Australia for recessive genetic disorders like cystic fibrosis, hemophilia, muscular dystrophy and sickle cell anemia or acquired genetic disorders like cancer or AIDS.

There are multiple ways for gene therapy like DNA recombination using vectors like plasmids, nanostructure or virus as they can invade cells and rectify the mutation. Despite its success rate there are a lot of challenges to administer gene therapy to a person. Identifying the specific body cells and accessing them, and later distributing the copies of the cells makes the process complex. There are two types of gene therapy: germline gene therapy, modifying the sperm and the egg which is passed down to the subsequent generations and somatic gene therapy, modifying the somatic cells of a person.

An ideal vector which is specific to the site, resistant to the immune system, anti- inflammatory and anti- allergen is used. The vector should be safe for the environment, patient, the doctor handling it, and work for the lifetime of the patient. The viral vectors though effective have certain drawbacks as they can be destroyed by the immune system of the patient or may cause cancer. Currently, gene therapy has been approached based on the size and efficiency  by viral vectors or physical mediators using nanotechnology like DNA microinjections, cationic polymers, cationic liposomes, and particle bombardment. 

Hematopoietic stem cells can be good target sites for gene therapy as they have a long life and reproduce more often. The genes can be transferred using induced pluripotent cells which differentiates further. It is efficiently used during the transplant of hepatocytes because of hepatitis which causes the failure of liver. Chimeric antigen recipient T (CAR-T) made by Eshhar and team, is a type of immunotherapy that manipulates the immune system to recognize and attack the T-cells in the tumor, which was later enhanced by adding CD28. The most recent CAR designs contain a fragment of an antibody, the CD3-ζ chain, and other stimulating molecules like CD134 or CD137. CAR-T immunotherapy may sometimes mistake a normal cell to be a malignant cell because of the presence of the same antigen. 

Clustered Regularly Interspaced Short Palindromic Repeats and Cas proteins (CRISPR-Cas) a leading biotechnological tool used for editing gene, gene inactivation, allele substitution  was first identified in Escherichia coli as repeated, variable sequences which were later identified as foreign DNA resulted due to memory against viral invasions found in bacteria’s adaptive immune system. Based on this technique, the CRISPR edits at specific sequences. The Cas9 nuclease, RNA, and the target DNA are the significant factors for the processing of this technique. The advancement in the CRISPR technology led to the translational trials in human somatic cells for therapeutic purposes. 

      

Germline gene therapy has been controversial for a few decades. Recently, Chinese researchers modified embryonic cells using CRISPR-Cas9. Though America is still waiting for a more efficient procedure, the United Kingdom approved its first project for healthy human embryo editing. 

         

In 1991, James Watson stated that the genes can be optimized, since then many developments in gene therapy have occurred. The induced pluripotent stem cells, CRISPR-Cas9, trials in germline gene therapy, types of vectors have been introduced and improved to expand the clinical application and enhance the safety.  When the pathological and surgical interventions do not help the patient, gene therapy has been helpful for patients with congenital diseases, cancer and monogenic disorders. Through multiple trials, and more preclinical studies gene therapy can be used in wider numbers with more safety. 

       

       

REFERENCE

Gonçalves GA, Paiva RD. Gene therapy: advances, challenges and perspectives. Einstein (Sao Paulo). 2017 Jul;15:369-75.

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