David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The re­searcher be­hind base-edit­ing is out with what some sci­en­tists are hail­ing as the biggest ad­vance­ment in CRISPR tech­nol­o­gy since that 2016 break­through: “prime edit­ing.” The new mol­e­c­u­lar gad­get is ca­pa­ble of eras­ing any base pair and sten­cil­ing in an­oth­er and cut­ting or adding long seg­ments of DNA with­out break­ing both strands of the he­lix.

Luke Dow Dow Lab

David Liu, base edit­ing pi­o­neer and founder of Beam Ther­a­peu­tics, pub­lished the find­ings in Na­ture along­side An­drew An­za­lone. They es­ti­mat­ed that the break­through “in prin­ci­ple” puts 89% of hu­man dis­eases in purview — al­though ex­perts cau­tioned that hu­man ther­a­pies were a long way off.

“This is a big ad­vance,” Luke Dow, a Cor­nell can­cer re­searcher who was not in­volved in the study,  told End­points News. “The ev­i­dence in this case for cor­rect­ing those dis­ease al­le­les is the first step and that’s a long way off from the last step.”

To piv­ot the tech in­to ther­a­peu­tic ap­pli­ca­tions, Liu al­so launched Prime Med­i­cine with the back­ing of Arch Ven­ture Part­ners, GV, New­path Part­ners and F-Prime.  That could spell trou­ble for Beam, which filed for a $100 mil­lion in Sep­tem­ber and may now see some of their sci­ence out­paced, al­though the prime edit­ing tech has been sub­li­censed to Beam for some fields.

The ear­ly CRISPR tech­nol­o­gy, for all its her­ald­ed pre­ci­sion, was some­thing of a blunt force ob­ject. It tears open DNA, cre­at­ing what are called dou­ble-strand breaks, and then leaves the DNA to patch it­self back up, by knit­ting the two strands to­geth­er, tak­ing ran­dom nu­cleotides from with­in the cell to fill the gap or splic­ing in patch­es of DNA sup­plied by sci­en­tists. It’s of­ten loathe to do the lat­ter, a ma­jor ob­sta­cle in ap­ply­ing CRISPR to dis­eases that re­quire not on­ly re­mov­ing faulty genes but putting in the right ones. Even when it does, it can of­ten cause off-tar­get ef­fects.

Liu made a ma­jor break­through in 2016 when he in­tro­duced base edit­ing – the abil­i­ty to di­rect­ly rewrite the nu­cleotides that make up DNA’s 4-let­ter al­pha­bet. News cov­er­age talked about the po­ten­tial to cure dis­eases such as sick­le cell, caused by a sin­gle nu­cleotide in the gene for he­mo­glo­bin.

The prob­lem was Liu’s first dis­cov­ery –and Beam Ther­a­peu­tics, the com­pa­ny he launched around it – had ma­jor dif­fi­cul­ty at­tack­ing sick­le cell, be­cause that first gad­get could on­ly make four switch­es: C-to-T, T-to-C, A-to-G, and G-to-A. A sick­le cell treat­ment would re­quire switch­ing T to A on the right gene.

In yes­ter­day’s Na­ture pa­per, Liu and his coau­thors switched T to A. They al­so switched every oth­er of the 12 pos­si­bil­i­ties.

“It doesn’t im­prove on base-edit­ing,” Dow said.  “The orig­i­nal base edit­ing tool the Liu lab de­scribed a few years ago with a few mod­i­fi­ca­tions be­came very ef­fi­cient. What this does is open up a lot of dif­fer­ent types of mu­ta­tions that weren’t avail­able pre­vi­ous­ly.

Liu de­scribed the new tech as a “search-and-re­place” tool – es­sen­tial­ly con­trol F for the hu­man genome. That’s prob­a­bly over­selling where the tech is to­day – Dow said they on­ly test­ed it on four hu­man cell types, leav­ing ques­tions on how it will fare in the rest – but it gets at the po­ten­tial. In ad­di­tion to sick­le cell, re­searchers spliced out the 4-let­ter se­quence that caus­es Tay-Sachs. Over­all, they made 175 ed­its in mouse and hu­man mod­els.

The au­thors re­port­ed be­ing able to do 44 in­ser­tions and said more was pos­si­ble. They al­so were able to ed­it in non-di­vid­ing such as neu­rons and liv­er cells.

Rather than break­ing the cell DNA on both sides and pro­vid­ing an­oth­er piece of DNA for the cell to in­cor­po­rate, the new tech­nol­o­gy breaks on­ly one strand and us­es RNA to sup­ply the nu­cleotides. By not caus­ing dou­ble-strand breaks, it lim­its off-tar­get ef­fects on oth­er parts of the genome – one of the big­ger risks of CRISPR tech­nol­o­gy.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

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AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

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Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

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Matt Kapusta, uniQure CEO

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De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

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Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

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John Leonard, Intellia CEO

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Intellia Therapeutics presented the much-anticipated data for its Regeneron-collaborated NTLA-2001 Friday morning, adding to the initial Phase I results it first delivered almost a year ago to the day.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”