#349: CRISPRme Adds Genetic Diversity To Genome Editing, & More

As biopharma companies use them to modify specific regions of the genome, CRISPR gene editing and base editing could transform the therapeutic landscape. Roughly a decade after CRISPR/Cas9’s seminal publications, the Food & Drug Administration (FDA) is in final review of CRISPR-based medicines to cure sickle cell disease and beta-thalassemia.

Like all classes of medicine, CRISPR-based therapies face obstacles, the most common of which is off-target editing in which CRISPR confuses its intended DNA target with a similar part of the genome. While often benign, off-target edits can be dangerous, so biopharma companies are using software tools and experimental tests to predict, assess, and manage the risks of off-target editing.

Recently, a group of researchers published an open-access software toolkit called CRISPRme that mitigates the risk of off-target editing. While many computational tools use a common human reference genome to predict off-target edits, CRISPRme is optimized for genetic variations from diverse ancestral groups. Importantly, the researchers illustrated that people of African ancestry could be at particular risk for off-target editing. Understanding the natural variation in a population can limit the off-target editing regions not represented in the single human reference.

Coupled with population sequencing projects from diverse geographies, tools like CRISPRme should help ensure that gene editing therapies will benefit all populations.

In 2015, Amazon held a “picking challenge” to identify a team that could develop the best robot to pick and place items from and in bins. The winner developed a robot that picked and placed 30 items an hour, as shown below, which was well below the ~400 items on average for humans. In September 2022, Amazon announced a prototype robot that picks 1,000 items per hour, a 33x increase in improvement in seven years, now outpacing humans.

ARK’s research suggests that advances in computer vision and deep learning have been responsible for much of the improvement. Amazon also has indicated that it is building ~1,000 warehouse robots per day in what appears to be a massive push into robotics.

[1] https://www.amazon.science/latest-news/pinch-grasping-robot-handles-items-with-precision; https://berkeleyautomation.github.io/dex-net/#dexnet_4; https://www.technologyreview.com/s/610587/robots-get-closer-to-human-like-dexterity/; https://arxiv.org/pdf/1610.05514.pdf; https://www.engadget.com/2015-06-01-amazon-picking-challenge-winner.html

Last week, the U.S. Securities and Exchange Commission (SEC) filed charges against Genesis Global Capital LLC and Gemini Trust Company LLC for offering and selling unregistered securities to retail investors through Gemini’s Earn product.

The action occurred in the middle of a Twitter dispute between the two companies. Gemini, led by the Winklevoss twins, and Genesis, a subsidiary of Barry Silbert’s Digital Currency Group, have been battling over the $900 million frozen on Genesis’s platform, potentially at the expense of Gemini’s 340,000 Earn users. Two months after Genesis halted withdrawals, both parties have yet to reach a resolution. While the SEC’s charges will not benefit creditors in the short term, Gemini could be forced to make its customers whole, potentially imperiling its business.

Gemini’s founder, Tyler Winkelvoss, has stated that the SEC’s charge is unfounded, unexpected, and motivated politically at the expense of investor protection. Others, including CEO of Signum Growth Capital, Angie Dalton, disagree, noting that the SEC set a precedent 16 months ago when it issued a Wells Notice[1] and prevented Lend, Coinbase’s product, from debuting. As Dalton points out, Coinbase’s Wells Notice should have been fair warning to competitors that their products were infringing on US federal securities laws.

This crisis raises a few vexing questions. Instead of Coinbase’s unlaunched Lend, why didn’t the SEC target Earn, the product that Gemini already had launched, which could have protected 340,000 investors from as much as $900 million in losses? Perhaps more important, why didn’t its legal counsel recommend that Gemini unwind Earn in response to Coinbase’s Wells Notice on Lend?

While Genesis has yet to comment on the charges, Gemini plans to defend itself aggressively, particularly because it received regulatory approval for Earn from the New York Department of Financial Services (NYDFS).

ARK will continue to monitor this situation closely as it unfolds.

[1] A Wells Notice is a letter that the SEC sends to people or firms when it is planning to bring an enforcement action against them.