Genome Editing: A Modern By-Pass To Evolution

Have you ever thought of whether you and I can be updated to their best and modern versions? Genome editing or Gene editing is a high profiling gene alteration mechanism indulging enzymes (nucleases) to cut DNAs in vivo, replace or delete the faulty sections and substitute it forever.

By Hafsa Adnan and Zoya Saleem

From 1856, after Mendel’s work the concept of gene exploited and since then the, whole idea has been to open up the boxes getting a new box inside. From concept to its practical repercussions, it has been applied to obtain transposed animals, fruits, crops, micro-organism; all suiting to our benefits. These modernized genes flow into generations embarking way to modern evolution as well.

Deletion, insertion and transposition are the three ways by which the genome can be edited. Adding on, inactivating a particular set of genes or activating the switched off ones has also been a beneficial approach. Genome modifications are obtained in two ways: in vitro and in vivo. In vivo requires adding in situ editing tools that precisely correct the DNA.

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genome-editing

ZFNs (Zinc finger nucleases), TALENS (Transcription activator-like effector nucleases) and the most versatile, cheap, easy-to-go CRISPR (clustered regularly interspaced short palindromic repeat-Cas-associated nucleases. These cut DNA at specific non-sequence sites forming Double stranded breaks (DSBs) which can be repaired inserting exogenous (Donor DNA) or endogenous DNA sections. The nucleases has site-specific DNA binding domains that cleave the target DNA, each nuclease differing with a hallmark of amino acid sequences and mechanism of interaction. The DSBs are repaired in two ways: Homologous DNA recombination (HDR) or Non-homologous end joining (NHEJ). HDR works for insertion, deletion and activation using donor DNA whereas NHEJ results in insertion or deletion in diverse target lengths and is more susceptible to frame shift mutations.

Revolutionary research can be seen on human genes only because of the ebullient evolution of gene editing. Moreover, it also enables researchers and readers to apprehend the role of gene in any disease. The idea of genetically engineered babies has led scientists dive deep into the sea of genome editing. Humans have been successfully given gene therapies, halting the familial disorders at a generation.

genome-editing

In cancer research hematopoietic stem cells (HSCs) and tumor-targeted T cells were genetically corrected. Cardiovascular Disease (CVD) deals with deep gene editing analysis of virulent genes and their molecular mechanism to check their capability of gene therapy and expression e.g. in coronary artery angiography a balloon catheter is coated with genes that can proliferate the artery forming a by-pass for blood flow. Metabolic diseases including obesity, diabetes, hypercholesterolemia and hyperlipidemia. Donor plasmid and Cas 9 sequences are micro-injected into the oocyte and pancreatic Beta cells are evaluated for insulin production. Familial hypercholesterolemia cures by ex-vivo therapy. Disease is due to lack of a receptor on liver to remove cholesterol, so a portion is excised and infected with retro-virus containing a gene for the receptor that incorporates into the human cell’s DNA and works by producing the receptor.

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Neurodegenerative diseases include accumulation of proteins owing to abnormal structures due to autophagic lysosomal pathways oxidative stress and circuit alternations signaling that NDs are caused by complicated interactions of multiple genetic factors. Huntington’s disease (HD), Alzheimer’s disease (AD), and Parkinson’s disease (PD) are being treated with gene therapy due to their not so efficient cure as yet. In Viral diseases analyzing the viral or host sequences, either the host genome (required by virus) is modified or the viral genome is inactivated genome editing-based HIV therapy involves modifying infectious genes to synthesize HIV-resistant CD4+ T cells and re-infusing them into patients.

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One of the most crucial and hot trend of genome editing is its use in immunotherapy for cancer. In this the person’s immune system is induced to fight against cancer itself. T-cells are genetically engineered after being collected from WBCs and known as chimeric antigen receptor (CAR) T cells, these target tumor-associated antigens could exaggerate the therapy response by being modified with tumor-antigen-specific receptors and then induced in the human blood.

Transgenic technologies have been developed at a pace over the past 10 years and have started to show extraordinary utility in various fields from basic research to applied biotechnology and biomedical clinical trials. The advances and research in field of genetics has been neglected in the past due to mere interference of religion. Inevitably genome editing has been exploited negatively on a large such as formation of deadly viruses but its undeniable vast range of humanly benefits cannot be ignored. We may not assume this as end of it for every new is a beginning of an end.  

References

https://www.nature.com/articles/s41392-019-0089-y#Sec2

https://www.yourgenome.org/facts/what-is-genome-editing

Pictures from:

https://www.nature.com/articles/s41392-019-0089-y#Sec2

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