In a break­through, Chi­nese re­searchers clone mon­keys hop­ing to pro­vide bet­ter dis­ease mod­els

Hua Hua (left) and Zhong Zhong (right), the first two mon­keys cre­at­ed by so­mat­ic cell nu­clear trans­fer.
Cred­it: Qiang Sun and Mu-ming Poo / Chi­nese Acad­e­my of Sci­ences

Two mon­keys are mak­ing head­lines around the world. Now bare­ly two months old, they might help lead the way down the path to some of the Holy Grails of bio­med­ical re­search — at least that’s the hope of their cre­ators.

Zhong Zhong and Hua Hua, the iden­ti­cal long-tailed macaques, were cre­at­ed at the Chi­nese Acad­e­my of Sci­ences In­sti­tute of Neu­ro­science in Shang­hai with the same method that gave birth to Dol­ly the sheep in 1996. Known as so­mat­ic cell nu­clear trans­fer, or SC­NT, it takes the nu­cle­us of a dif­fer­en­ti­at­ed cell from one an­i­mal and in­fus­es it in­to an emp­ty egg cell from an­oth­er. An elec­tric cur­rent trig­gers the egg to de­vel­op in­to an ear­ly em­bryo, and the re­sult­ing fe­tus, grown in a sur­ro­gate, would be a repli­ca of the an­i­mal that do­nat­ed the nu­cle­us.

Sci­en­tists have cloned more than 20 species this way, but cloning pri­mates re­mained a unique chal­lenge. Pre­vi­ous at­tempts have nev­er pro­gressed be­yond the ear­ly em­bryo stage.

The break­through here was the in­tro­duc­tion of two mod­u­la­tors — specif­i­cal­ly, Kdm4d mR­NA and a hi­s­tone deacety­lase in­hibitor called tri­cho­statin A — in the one-cell stage that switched on or off a num­ber of genes that were af­fect­ing em­bryo de­vel­op­ment.

From there, the re­searchers yield­ed what they hope to be the first of many ge­net­i­cal­ly uni­form mon­key mod­els that, com­bined with gene edit­ing tools, could shed light on dis­ease mech­a­nisms and of­fer ther­a­peu­tic test­ing ground for dis­eases that have elud­ed hu­man un­der­stand­ing, such as Alzheimer’s and Parkin­son’s. Those are ar­eas where mice mod­els have proven woe­ful­ly in­ad­e­quate in terms of pre­dict­ing hu­man re­ac­tions to drugs; mul­ti­ple oth­er ge­net­ic dis­eases could al­so be tar­gets.

But — as one would rea­son­ably ex­pect — this cloning suc­cess car­ries im­por­tant caveats. First off, it ba­si­cal­ly on­ly works in fe­tal cells. While two ba­bies were born us­ing adult mon­key cu­mu­lus, they were both short-lived and one had ab­nor­mal body de­vel­op­ment.

Fur­ther­more, the low suc­cess rate means pro­duc­ing a pop­u­la­tion of cloned mon­keys large enough to be ef­fec­tive would re­quire an ex­po­nen­tial­ly larg­er num­ber of em­bryos and sur­ro­gates. At that scale, the prac­ti­cal and eth­i­cal ques­tions al­ready sur­round­ing pri­mate re­search would like­ly snow­ball in­to some­thing even big­ger.

To put things in­to per­spec­tive, Zhong Zhong and Hua Hua were the on­ly lucky ones from six preg­nan­cies from 21 sur­ro­gates with 79 im­plant­ed em­bryos be­tween them. An ad­di­tion­al 22 preg­nan­cies were con­firmed among 42 sur­ro­gates in the adult cell group.

So no, cloned mon­keys are not com­ing to a lab near you any­time soon. But it’s sure to set off — and it al­ready has — a flur­ry of de­bate and, pos­si­bly, new re­search.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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Image: Shutterstock

MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.

Dermavant Sciences' first consumer TV ad for its Vtama psoriasis med shows people ready for a new topical treatment.

Roivant’s Der­ma­vant de­buts first-ever TV com­mer­cial for pso­ri­a­sis cream Vta­ma

Dermavant Sciences has been marketing its first product, psoriasis med Vtama, to dermatologists for months, but on Tuesday it rolled out its first consumer campaign. The debut DTC effort including a streaming TV commercial encourages patients to a “Topical Uprising” in a nod to Vtama being a topical cream.

In the new commercial, a swell of people discards scarves and jacket coverings, gathering in the street to converge on a pharmacy to demand a steroid-free prescription. A moment of levity follows when a pharmacist says, “You know you can just talk to your doctor, right?” The gathered crowds collectively says, “Oh.”

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FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.

Andrew Phillips, Nexo Therapeutics CEO

Scoop: Ver­sant, NEA launch new biotech helmed by ex-CEO of pro­tein de­grad­er C4 Ther­a­peu­tics

Long-time biotech venture firms Versant and New Enterprise Associates are backing a new startup run by former C4 Therapeutics chief executive Andrew Phillips.

The fledgling biotech has raised at least $30 million so far, according to paperwork filed with the SEC this week. The round could balloon to $60 million.

Phillips, who left protein degradation startup C4 in 2020 to be a managing director at Cormorant Asset Management, is running the show of the new venture as president, the SEC filing outlines. He also served as interim CEO of Cormorant-backed and Hansoh Pharmaceutical-partnered Blossom Bioscience last year.

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