Gene-editing: The Revolution has begun.

Surupa Chakraborty, Amity University Kolkata

The 21^st century witnessed one of the major scientific breakthroughs when scientists revealed the development of a biological tool called CRISPR/Cas9 that can enable us to rewrite or edit the DNA of existing genomes. Ever since then, highly targeted gene editing has been made possible which could potentially revolutionize the field of medical science. With the advent of such cutting edge gene-editing technologies like CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats), TALENS(Transcription Activator-Like Effector Nucleases), and ZFN(Zinc Finger Nucleases), scientists can now target and make desirable alterations in very specific areas within the genome.

They can induce double-stranded DNA breaks and make single-letter changes that can behold promising applications in treating many diseases linked with genetic variations. These methods are based on different types of enzymes called nucleases that have specific genetic composition allowing them to target and latch onto the DNA of our interest. They are a part of the bacterial defence system and act like molecular scissors to cut any part of the genome with unparalleled accuracy.

Challenges

As the quest for high-efficiency gene-editing technology continues further, biologists express their grave concerns over more precision of genetic alterations, the prospect of editing germ-line cells, side effects, risks of bio-hackers, and ethical issues. However, the concept of gene editing has flourished over the years and is now being pursued by researchers, academics, and the leading industries in this field to understand how genetics may impact disease and to develop new types of antimicrobials and anti-virals and therapies for incurable diseases such as cancer. The moral, ethical, and technological concerns might be eventually resolved with more advances in genetic engineering.

Recent advances

Many potential genome editing technologies are in the pipeline to treat several rare, hereditary, or incurable diseases.

• Despite the ethical concerns, Russian biologist Denis Rebrikov has revealed that he plans to use CRISPR genome editing to correct the inherited hearing loss mutation in the GJB2 gene so that a normal baby is born to a deaf couple.
• Sabine Fuchs’s lab recently used “prime editing” to correct DGAT1 deficiency in intestinal organoids and in liver organoids to correct ATP7B mutation that causes Wilson’s disease. The whole-genome sequencing of the prime-edited organoids revealed the absence of genome-wide off-target effects implying the immense therapeutic potential of this precise gene editing.
• EDIT-301 therapy, developed by Editas Medicine has been promising in recent preclinical studies in which CD34+ cells are collected from a patient, genetically edited using CRISPR-Cas12a (Cpf1), and then returned to the patient to treat sickle-cell disease. 
• Two (chimeric antigen receptor) CAR T-cell therapies are known as Kymriah and Yescarta, have been recently approved by the FDA which are being commercialized by Novartis and Gilead Sciences, respectively. To overcome the challenges associated with the allogeneic CAR T-cells, appropriate strategies like multiplex genome engineering and nonviral CRISPR editing systems have been implemented. 

The possibilities seem to be endless. However, we will never know the true potential of gene editing until we have access to deeper scientific expertise in this field.

Also read: Appendicitis – Antibiotics or Appendectomy?

Sources:

• Prime editing for functional repair in patient-derived disease models, Imre F. Schene, Indi P. Joore, Michal Mokry, Anke H.M. van Vugt, Peter M. van Hasselt, Edward E.S. Nieuwenhuis, Sabine A. Fuchs, 2020, Biorxiv, https://doi.org/10.1101/2020.06.09.139782.
• EDIT-301: An Experimental Autologous Cell Therapy Comprising Cas12a-RNP Modified mPB-CD34+ Cells for the Potential Treatment of SCD, Edouard De Dreuzy , Jack Heath et al.,Blood (2019) 134 (Supplement_1): 4636,https://doi.org/10.1182/blood-2019-130256
• CRISPR-engineered T cells in patients with refractory cancer. Stadtmauer EA, Fraietta JA, Davis MM, et al. Science 2020; 367(6481): eaba7365,https://doi.org/10.1126/science.aba7365

• The Corrosion Prediction from the Corrosion Product Performance
• Nitrogen Resilience in Waterlogged Soybean plants
• Cell Senescence in Type II Diabetes: Therapeutic Potential
• Transgene-Free Canker-Resistant Citrus sinensis with Cas12/RNP
• AI Literacy in Early Childhood Education: Challenges and Opportunities