Is CRISPR Caus­ing Con­cern?

BioSpectrum (India) - - BIO CONTENT - Dr Man­beena Chawla man­beena.chawla@mmac­

Since its dis­cov­ery in 2012, the gene edit­ing tool CRISPR-Cas9 has gen­er­ated quite an ex­cite­ment by mak­ing the pos­si­bil­ity of rou­tine genome edit­ing a re­al­ity. A num­ber of biotech com­pa­nies, in­clud­ing CRISPR Ther­a­peu­tics, In­tel­lia Ther­a­peu­tics, Edi­tas Medicine, and eGe­n­e­sis, are cur­rently de­vel­op­ing medicines based on this tech­nol­ogy. In ad­di­tion, CRISPR-based tech­nol­ogy is al­ready be­ing used in the clin­i­cal con­text in China. For ex­am­ple, at Hangzhou Cancer Hos­pi­tal, im­mune cells of pa­tients with oe­sophageal cancer are be­ing reengi­neered to fight the dis­ease.

But lately an ar­ti­cle pub­lished in Na­ture Biotech­nol­ogy has led to a de­bate over the safety of the po­ten­tial CRISPRbased ther­a­pies. Stud­ies have high­lighted that CRISPR-Cas9 edited cells might trig­ger cancer. It is likely that this find­ing can dras­ti­cally af­fect the ac­cu­racy of gene edit­ing and cause al­ter­ations of non-tar­get genes, lead­ing to con­cerns that if used clin­i­cally, CRISPR-Cas9 gene edit­ing could re­sult in un­wanted dam­age in hu­mans, or worse, tu­mor for­ma­tion.

“CRISPR tech­nol­ogy is a pow­er­ful tech­nol­ogy in gene edit­ing and could an­swer a lot in the field of ge­netic dis­or­ders. How­ever, we do not yet fully un­der­stand gene in­ter­ac­tions and that could only come with new knowl­edge which is be­ing gen­er­ated. We need to gather enough ev­i­dence through ex­per­i­ments be­fore reach­ing any con­clu­sion”, shares Dr N K Ganguly, For­mer DG, In­dian Coun­cil of Med­i­cal Re­search.

The ma­jor safety con­cern is that, this field is mov­ing so quickly and some re­searchers want to get into hu­man clin­i­cal tri­als right away, even be­fore the CRISPR tech­nol­ogy par­a­digm has been fully val­i­dated. Re­searchers in China have ac­tu­ally pro­ceeded to hu­man clin­i­cal tri­als us­ing CRISPR much faster than has been pos­si­ble in the United

States. Re­cent re­ports state that some­where be­tween 80 and 100 peo­ple are al­ready be­ing tried, or al­ready be­ing tested us­ing CRISPR.

“Much of the ba­sic re­search around the CRISPR-Cas9 sys­tem has cen­tered around two themes. The first has been to en­sure speci­ficity of the sys­tem so that the mod­i­fi­ca­tions are made only in the de­sired ge­nomic re­gion and not any­where else in the genome. The sec­ond theme cen­tres on the na­ture of mod­i­fi­ca­tion. Knock­ing out a gene by caus­ing dou­blestranded DNA breaks is the most com­mon tech­nique, but the sys­tem is very ver­sa­tile and it has been used for ev­ery­thing from gene edit­ing to con­trol­ling gene ex­pres­sion. These tech­niques con­tinue to be op­ti­mized and the costs have re­duced to a point that has democra­tised re­search in the field. How­ever, the im­pli­ca­tions of car­ry­ing out these changes in hu­mans are far from clear”, points out Dr Vamsi Veera­macha­neni, Chief Sci­en­tific Of­fi­cer, Strand

Life Sciences.

No mat­ter which side wins, it is ev­i­dent that years will go by be­fore the CRISPR sys­tem is ready for prime time and clin­i­cal use. “Fully achiev­ing the prom­ise of this tech­nol­ogy will be achieved with more knowl­edge and un­der­stand­ing of the genomeed­it­ing mech­a­nism sup­ported by sci­en­tific peer re­view and the rigor and reg­u­la­tions ap­plied to clin­i­cal tri­als”, men­tions Supriya Shivaku­mar, Head of strat­egy, Gene Edit­ing & Novel Modal­i­ties, Merck.

How­ever, the safety con­cerns sur­round­ing CRISPR-based gene edit­ing are less of a con­cern in po­ten­tial agri­cul­tural ap­pli­ca­tions in which the tech­nol­ogy could also have im­por­tant im­pli­ca­tions.

“This tech­nol­ogy has tremen­dous po­ten­tial in agri­cul­ture and ma­nip­u­la­tions in Syn­thetic Bi­ol­ogy. Ben­e­fi­cial ef­fects in corn, potato and tomato have al­ready been shown. The big­gest prob­lem could still be reg­u­la­tion, es­pe­cially in In­dia. In­dia needs to move fast in terms of ush­er­ing in a sec­ond green revo­lu­tion us­ing such tech­nolo­gies in a trans­par­ent man­ner. It should not get into the mud­dle be­ing ex­pe­ri­enced with the ap­pli­ca­tion of GM tech­nol­ogy. A pro-ac­tive ini­tia­tive to draw guide­lines for use of CRISPR and its com­mer­cial­iza­tion in agri­cul­ture is a pri­or­ity. An early suc­cess in pro­duc­ing Be­tac­arotene-rich ba­nana in In­dia is a dis­tinct pos­si­bil­ity”, high­lights Pro­fes­sor G. Pad­man­a­ban, NASI Plat­inum Ju­bilee Se­nior Sci­en­tist, Depart­ment of Bio­chem­istry, In­dian In­sti­tute of Science (IISc).

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