基因編輯已經不存在CRISPR治療了嗎？

StephenW

Is Gene Editing Already Leaving CRISPR Therapeutics Behind?
Innovative companies are trying to ensure that CRISPR Therapeutics' foothold in gene editing doesn't last forever.
Jason Hawthorne
Jason Hawthorne
(TMFjbonefish)
Nov 21, 2020 at 6:33AM

In hindsight, one could say the iPhone basically invented the smartphone market with its interactive touch screen, internet-surfing capabilities, app store, and camera. Except it didn't. The LG Prada, released in 2006, had a camera, apps, a web browser, and the same type of touchscreen as the iPhone. LG had the technology right, but another company came along and simply did it better. A similar dynamic might now be playing out in the world of gene editing.

Although there are three main gene-editing tools being used today, CRISPR, which stands for "clustered regularly interspaced short palindromic repeats," has become the most widely used due to its simplicity and versatility. One of the publicly traded companies using CRISPR to develop treatments for diseases is CRISPR Therapeutics (NASDAQ:CRSP). Despite the acceptance of CRISPR-Cas9 as the standard system for gene editing, new methods are being discovered that could make CRISPR Therapeutics' Cas9 methodology the LG Prada of the gene-editing world.
A double helix DNA strand with a piece missing and a gloved-researcher inserting the missing piece.

Image source: Getty Images.
Keeping your eye on the ball

Jennifer Doudna, a biochemist at the University of California, Berkeley, and Emmanuelle Charpentier, who headed a lab at the University of Vienna, first published evidence that CRISPR could cut targeted DNA in June 2012. But a patent filed seven months later by the Broad Institute of MIT and Harvard tried to undercut the pair's exclusive claim to commercialize the approach by outlining a more specific description of the process in the cells that make up plants, animals, and humans.

Despite the dispute over patents and licensing revenues, Doudna and Charpentier won the 2020 Nobel Prize in Chemistry for discovering the gene-editing capabilities of bacteria using CRISPR-Cas9. Today, Doudna is associated with Intellia Therapeutics (NASDAQ:NTLA) and Caribou Biosciences, while Charpentier is associated with several companies including CRISPR Therapeutics. Another publicly traded company, Editas Medicine (NASDAQ:EDIT), was originally founded by Doudna, but is now associated with the Broad Institute patent claim.

While the battles in court continue to this day, other companies are finding new CRISPR tools that may be even more effective at editing genes in some circumstances. The foundational tool, CRISPR-Cas9, makes a blunt double-stranded DNA break. One drawback of this approach is a propensity to occasionally make cuts at unintended sites in the DNA. Although additional engineering has largely overcome this, it's a frightening possible side effect. CRISPR-Cas12 was the next widely accepted tool. This method makes staggered cuts and can edit epigenomes -- the chemical compounds that can tell genes to turn on or off. Cas13 influences gene expression by targeting RNA instead of DNA. However, more recent research has discovered CasX and CasY. CRISPR-CasX is smaller than Cas9 and can be used to control gene expression, not just to edit genes. CasY acts much like Cas9, but is made of a completely different protein structure, allowing it to function in different conditions.
New tech trying to leapfrog old tech

In 2017, Excision BioTherapeutics was the first to obtain an exclusive license for the new CasX and CasY gene editors from Jennifer Doudna's lab at UC Berkeley. In March, the company used the Cas9 tool to successfully remove simian immunodeficiency virus (SIV) genomes from monkeys. SIV is an HIV-like virus that affects monkeys; removing the virus' genome eliminates its ability to infect cells. Excision is also working on gene-based approaches for treating herpes and a rare central nervous system disease. And the company is applying the CasX and CasY tools for its work on hepatitis B and COVID-19, respectively. Other than its work on HIV, none of the company's treatments are expected to start in clinical trials before 2022.

For now, CRISPR Therapeutics is safe. The company's pipeline is currently targeting beta thalassemia and sickle cell disease -- diseases caused by a single gene defect, ideal for the Cas9 approach -- and multiple immune cell products designed to attack cancer cells. Despite the advances in new gene-editing methods, even Excision BioTherapeutics is relying on the Cas9 tool in most of its clinical studies.
Don't get too comfortable

Investors in CRISPR Therapeutics and other gene-editing companies like Intellia Therapeutics and Editas Medicine shouldn't get complacent. When investing, it's easier to understand faster and cheaper technology in computing or consumer products. Just because these advances are in biology doesn't mean the same rules won't apply. Researchers will continue to find better and cheaper ways of manipulating genomes to treat and cure diseases. The fact that a small start-up managed to grab an exclusive license from the Nobel Prize-winning lab that practically invented gene editing should raise alarm. Savvy shareholders will look out for indications that the CasX and CasY tools are being applied in areas once assumed to be the domain of CRISPR Therapeutics' and its Cas9 methods.

Jason Hawthorne has no position in any of the stocks mentioned. The Motley Fool owns shares of and recommends CRISPR Therapeutics and Editas Medicine. The Motley Fool has a disclosure policy.

StephenW

基因編輯已經不存在CRISPR治療了嗎？
創新公司正在努力確保CRISPR Therapeutics在基因編輯中的立足點不會永遠持續下去。
傑森·霍桑（Jason Hawthorne）
傑森·霍桑（Jason Hawthorne）
（TMFjbonefish）
2020年11月21日上午6:33

事後看來，可以說iPhone基本上是通過其交互式觸摸屏，上網功能，應用商店和相機發明了智能手機市場。除非沒有。 LG Prada於2006年發布，具有相機，應用程序，網絡瀏覽器以及與iPhone相同類型的觸摸屏。 LG擁有這項技術，但是另一家公司也加入進來，只是做得更好。現在，基因編輯領域可能正在發揮類似的作用。

儘管今天使用了三種主要的基因編輯工具，但由於其簡單性和多功能性，CRISPR代表著“聚簇的規則間隔的短回文重複序列”，已成為使用最廣泛的工具。使用CRISPR開發疾病治療方法的一家上市公司之一是CRISPR Therapeutics（NASDAQ：CRSP）。儘管人們接受了CRISPR-Cas9作為基因編輯的標準系統，但仍發現了使CRISPR Therapeutics的Cas9方法成為基因編輯領域的LG Prada的新方法。
一條雙螺旋DNA鏈缺失了一條，戴著手套的研究人員將缺失的那條插入。

圖片來源：Getty Images。
盯著球

加利福尼亞大學伯克利分校的生物化學家詹妮弗·杜德納（Jennifer Doudna）和維也納大學實驗室的負責人艾曼紐·夏龐蒂埃（Emmanuelle Charpentier）首次發表證據表明CRISPR可以在2012年6月切割目標DNA。但是七個月後，Broad申請了一項專利。麻省理工學院和哈佛研究所試圖通過概述組成植物，動物和人類的細胞中的過程的更具體描述，來削弱該夫婦將該方法商業化的專有權利。

儘管在專利和許可收入方面存在爭議，Doudna和Charpentier因利用CRISPR-Cas9發現細菌的基因編輯能力而獲得了2020年諾貝爾化學獎。如今，Doudna與Intellia Therapeutics（NASDAQ：NTLA）和Caribou Biosciences相關，而Charpentier與包括CRISPR Therapeutics在內的多家公司相關。另一家公開上市的公司Editas Medicine（NASDAQ：EDIT）最初由Doudna創立，但現在與Broad Institute的專利主張有關。

雖然今天的法庭鬥爭仍在繼續，但其他公司正在尋找新的CRISPR工具，在某些情況下，這種工具在編輯基因方面可能更加有效。基本工具CRISPR-Cas9使鈍的雙鏈DNA斷裂。這種方法的一個缺點是傾向於偶爾在DNA中意外的位置進行切割。儘管其他工程已在很大程度上克服了這一問題，但這是一個令人恐懼的副作用。 CRISPR-Cas12是下一個被廣泛接受的工具。這種方法可以進行交錯切割，並可以編輯表觀基因組（epigenomes）-可以告訴基因開啟或關閉的化學化合物。 Cas13通過靶向RNA而不是DNA來影響基因表達。但是，最近的研究發現了CasX和CasY。 CRISPR-CasX比Cas9小，可用於控制基因表達，而不僅僅是編輯基因。 CasY的行為與Cas9十分相似，但它由完全不同的蛋白質結構組成，因此可以在不同條件下發揮作用。
新技術試圖超越舊技術

2017年，Excision BioTherapeutics率先從加州大學伯克利分校的珍妮弗·杜德納（Jennifer Doudna）的實驗室獲得了新的CasX和CasY基因編輯器的獨家許可。 3月，該公司使用Cas9工具成功地從猴子身上移除了猿猴免疫缺陷病毒（SIV）基因組。 SIV是一種會感染猴子的類似HIV的病毒；刪除病毒的基因組會消除其感染細胞的能力。 Excision還正在研究基於基因的方法來治療皰疹和罕見的中樞神經系統疾病。該公司正在將CasX和CasY工具分別用於乙型肝炎和COVID-19的研究。除了在艾滋病毒方面的工作外，預計該公司的任何療法都不會在2022年之前開始臨床試驗。

就目前而言，CRISPR Therapeutics是安全的。該公司的產品線目前針對的是β地中海貧血和鐮狀細胞疾病-一種由單一基因缺陷引起的疾病，是Cas9方法的理想選擇-以及旨在攻擊癌細胞的多種免疫細胞產品。儘管新的基因編輯方法取得了進步，但Excision BioTherapeutics的大部分臨床研究都依賴於Cas9工具。
別太舒服
CRISPR治療公司和其他基因編輯公司如Intellia Therapeutics和Editas Medicine的投資者不應自滿。 投資時，更容易理解計算或消費產品中更快，更便宜的技術。 僅僅因為這些進展是生物學上的，並不意味著相同的規則將不適用。 研究人員將繼續尋找更好和更便宜的方法來操縱基因組來治療和治癒疾病。 一家小型初創企業成功獲得了諾貝爾獎得主實驗室的獨家許可，該實驗室實際上發明了基因編輯，這一事實應該引起警覺。 精明的股東將尋找跡象表明，CasX和CasY工具已被用於曾經被認為是CRISPR Therapeutics'及其Cas9方法領域的領域。

傑森·霍桑（Jason Hawthorne）在任何上述股票中均無倉位。 Motley Fool擁有CRISPR Therapeutics和Editas Medicine的股份並向其推薦。 雜色傻瓜有一項披露政策。

StephenW

https://www.fool.com/investing/2 ... crispr-therapeutic/