Review implications of CRISPRCas9 and Human genome

Review article

Ethical implications of Controlled genome editing by CRISPR*-Cas9 System

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Sajida Jamshaid *

Department of Genetics, Virtual University, Pakistan

Abstract:

In future Genome editing technologies will have therapeutic potential for various incurable diseases i.e. cancer and genetic disorders. The genome editing platforms currently in use have revolutionized the field of genetics. At an accelerating rate these tools are entering areas with direct impact on human beings. We discuss here applications in agriculture, in medicine and Challenges, concerns and ethical implications of CRISPRCas9 and Human genome editing.

Keywords: CRISPR-Cas, Therapeutic potential, Genome editing etc.

Introduction:

 The introduction of CRISPR tools takes place in 2012. The power of these technologies allows direct modification of specific DNA sequences at their normal chromosomal locations including changes as small as a single base pair or large deletions, insertions or translocations. It is used to produce models of human disease in experimental organisms and fundamental gene function. 1

CRISPR-Cas9 is a genome editing tool which is used to target a particular deleterious and disease causing gene in certain genetic disorders. The targeted genes are altered that brings about the changes in the germline to the next generation so that the disease causing genes can be completely eradicated.

The impact of genome editing takes place on the security world food supply and   therapies. The important uses of it in agricultural and clinical evidences and many social issues were recognized by this technology. 1

It allows the modification of any part in the genome of an organism. The modifications depends upon the DNA repair capabilities of the cells in which the breaks are made 2.

Systemic academic review:

Applications in agriculture:

The current world food supply is inadequate and the situation will get worse as populations continue to grow. There are various considerations that are demands on water supplies that is uncertain about changing climates and animal welfare. Genome editing will not provide general solutions to these issues but there are some areas where the technology can help us. 3

It has important Applications to improve plants as well as crops it provide nutrition for the world population. Through genome editing improvements takes place in nutritional values in many species. 4

In the study related to livestock genome editing applied there so specific applications are still emerging. One example which is currently used is the genetic dehorning of dairy cattle 5.

Because the cattle are kept in close quarters dairy farmers typically remove their horns by physical methods that are painful and expensive. Natural genetic variants that are called polled exist in some beef breeds 6.  

This trait could be transferred to dairy herds by traditional breeding but it would be time consuming and so expensive to do so as it would be necessary to perform extensive additional breeding to restore favorable dairy traits. 7

Genetically engineered organisms and their regulation:

Genome edited animals and plants are genetically modified organisms GMOs but they differ from the controversial genetically engineered crops currently under cultivation. The latter carry transgenes imported from other species obtained from bacteria. By contrast genome editing allows the precise inactivation of an endogenous gene the conversion of an existing allele to a more favorable one or the precise insertion of an identified variant into additional breeds. The animal and plant products of these modifications are essentially identical to ones that could and in some cases do occur naturally or could be created by traditional breeding methods.

Genome editing like its less efficient predecessors is touted by some for its potential to clear deleterious traits from the family line and criticized by others for its echoes of simplistic and cruel notions of genetic superiority and inferiority.

Germline modification causes genetic changes to the embryos changes that are heritable this technique can have unpredictable effects to the future generations. Moreover unethical uses of the technique could emerge from gene editing of the human embryos. 11

The biology and therapeutic potential of CRISPR-Cas9:

In 2013 Feng Zhang opened the window through which genome editing became a therapeutic possibility 12 when he engineered a novel version of CRISPR-Cas9 to edit human genomes 13.

The speed and efficiency of CRISPR-Cas9 is a remarkable leap in research. This feature can enable it to increase the identification of genes that are associated with human diseases and facilitate the development of therapies to correct the mutated gene 14.

Due to its unparalleled genetic specificity scientists are using CRISPR-Cas9 genomic editing technology to facilitate discoveries in cancer biology. Cancer models have been developed using CRISPR-Cas9. 12.

Discussion:

Challenges, concerns and ethical implications of CRISPRCas9 Human genome Editing:

Genome editing in human embryos using CRISPR-Cas9 could have unpredictable effects to the future generations. CRISPR-Cas9 technology could be used for non therapeutic modifications. This procedure will open the door to the loss of human diversity and eugenics 15.

The nuclease may not be as efficient. The nuclease may not necessarily cleave both copies of the target gene or the cells may start dividing before the corrections are completed resulting in genetic mosaic. Mosaicism is frequently masked. Mosaicism causes major phenotypic changes and reveal expression of lethal genetic mutations 16. Some of the genetic disorders results from mosaicism include Down syndrome, Klinefelter syndrome and Turner syndrome.

Conclusion:

While CRISPR-Cas9 genome editing technology holds promise to personalized medicine, human genetic modification and the development of new drugs, the technology has raised caution flags. Genome editing technology is a cautionary tale. We can easily get caught up in the glamour of scientific and technological advancement while at the same time oblivious to the ethical ramification of such scientific and technological advancement.

Some scientists have expressed concern that human germline editing has not only crossed the ethical redline. The recent research by Chinese scientists using it to edit the embryo genome was not completely successful but had to be abandoned at its preliminary stage.

These off target mutations can be deleterious as they can cause cell death and transformation.  Embryo germline editing could be exploited in nontherapeutic research. For example it can be used to produce designer babies by eliminating undesired qualities and replaced them with desired ones.

Genome editing technology should not hinder the promising area of therapeutic development are involved in making genetic changes in somatic cells. Due to it challenges and ethical concerns raised by genome editing technology a temporary moratorium should be called on the technology to allow scientific community and to engage in a broad discussion to map the way forward for this technology.

Ethical considerations:

Despite the plethora of other applications much of discussion about this gene has focused on its potential for editing the nuclear DNA of human gametes are called germline editing. The critiques largely break down into two large categories that are used in ethical analyses of many different kinds of technologies and human actions. 8

 

References:

1 Dana Carroll and R. Alta Charo, The societal opportunities and challenges of genome editing in Genome Biology (2015) 16:242 DOI 10.1186/s13059-015-0812-0

2 Carroll D. Genome engineering with targetable nucleases. Annu Rev Biochem. 2014;83:409–39.

3  Foley JA, Ramankutty N, Brauman KA, Cassidy ES, Gerber JS, Johnston M, et al. Solutions for a cultivated planet. Nature. 2011;478:337–42.

4 Baltes NJ, Voytas DF. Enabling plant synthetic biology through genome    engineering.Trends Biotechnol. 2015;33:120–31.

5 Tan WS, Carlson DF, Walton MW, Fahrenkrug SC, Hackett PB. Precision editing of large animal genomes. Adv Genet. 2012;80:37–97.

6 Medugorac I, Seichter D, Graf A, Russ I, Blum H, Göpel KH, et al. Bovine polledness – an autosomal dominant trait with allelic heterogeneity. PLoS One. 2012;7, e39477.

7 Tan W, Carlson DF, Lancto CA, Garbe JR, Webster DA, Hackett PB, et al. Efficient nonmeiotic allele introgression in livestock using custom endonucleases. Proc Natl Acad Sci U S A. 2013;110:16526–31.

8 Portmore DW. Commonsense consequentialism: wherein morality meets rationality. New York: Oxford University Press; 2011.

9 Otieno MO (2015), CRISPR-Cas9 Human Genome Editing: Challenges, Ethical Concerns and Implications in J Clin Res Bioeth 2015, 6:6 DOI: 10.4172/2155-9627.1000253

10 Krishan K, Kanchan T (2015) Human genome editing and ethical considerations. Sci Eng Ethics.

11 Cyranoski D, Reardon S (2015) Chinese scientists genetically modify human embryos Nature News.

12 Chin A (2015) CRISPR-Cas9 Therapeutics: A Technology Overview. Oxford Biotechnolgy.

13 Cong L, Ran FA, Cox D, Lin S, Barretto R, et al. (2013) Multiplex Genome Engineering Using CRISPR/Cas Systems. Science 339: 819-823.

14 Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS (2013) “Repurposing CRISPR as an RNA- Guided Platform for Sequence- Specific Control of Gene Expression.” Cell 152: 1173-1183.

15  Lanphier E, Urnov F, Haecker SE, Werner M, Smolenski J (2015) Don’t edit the human germ line. Nature 519: 410-411.

16 Youssoufian H, Pyeritz RE (2002) Mechanisms and consequences of somatic mosaicism in humans. Nature Reviews Genetics 3: 748-758.

17 Rath D, Amlinger L, Rath A, Lundgren M (2015) The CRISPR-Cas immune system: biology, mechanisms and applications. Biochimie 117: 119-128.

18  Carroll D (2014) Genome engineering with targetable nucleases. Annu Rev Biochem 83: 409-439.

19 Cong L, Ran FA, Cox D, Lin S, Barretto R, et al. (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339: 819-823.

20  Mali P, Esvelt KM, Church GM (2013) Cas9 as a versatile tool for engineering biology. Nat Methods 10: 957-963.

21 Ma Y, Zhang L, Huang X (2014) Genome modification by CRISPR/Cas9. FEBS J 281: 5186-5193.

22 Nekrasov V, Staskawicz B, Weigel D (2013) Targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease. Nat Biotechnol 31: 691-693.

23 Luo X, Li M, Su B (2016) Application of the genome editing tool CRISPR/Cas9 in non-human primates. Zoolog Res 37: 241-219.

24 Zhang F, Wen, Guo X (2014) CRISPR/Cas9 for genome editing: progress, implications and challenges. Hum Mol Genet 23: R40-46.

25 Koo T, Lee J, Kim JS (2015) Measuring and reducing off-target activities of programmable nucleases including CRISPR-Cas9. Mol Cells 38: 475-481.

 

 

 

 

 

 

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