\u201cIt\u2019s incredibly exciting, and also comes with a heavy sense of responsibility, to make sure that \u2014 to the extent humanly possible \u2014 we have done everything we can to make these agents as safe and effective as possible for use in patients,\u201d Liu said.\u00a0<\/p>\n
Hundreds of millions of people worldwide suffer from genetic diseases. To help them, Liu, with support from the NIH, DARPA, and other federal agencies, has built on and looked beyond CRISPR-Cas9, the transformative gene-editing protein found in bacteria that cuts through DNA like scissors.\u00a0<\/p>\n
\u201cThat approach of cutting the DNA double helix is very useful for gene disruption or deletion,\u201d he said. \u201cBut if your goal is to correct a mutation that causes a genetic disease, it\u2019s not easy to use scissors to achieve gene correction.\u201d\u00a0<\/p>\n
The limits of the \u201cscissors\u201d approach led Liu and his team, including former postdocs Alexis Komor and Nicole Gaudelli, to develop two new approaches to gene editing: base editing and prime editing. Base editing works on the four nucleotide bases of a DNA strand \u2014 A, C, G, and T \u2014 rather than on the entire double helix.<\/p>\n
\u201cYou can change a C to a T, a T to a C, an A to a G, or a G to an A,\u201d Liu said. \u201cAnd those happen to be four of the most common kinds of mutations that cause genetic diseases.\u201d\u00a0<\/p>\n
But what about genetic diseases caused by other kinds of single-letter swaps, or by unwanted extra letters, or by missing DNA letters? For those cases, Liu\u2019s team, including former postdoc Andrew Anzalone, developed prime editors. Liu likened the tool to a word processor, able to search out a flawed piece of DNA and replace it with a synthesized DNA flap that is specified by the user.\u00a0<\/p>\n
\n\u201cThere was no knowledge of what CRISPR did, or whether it was going to be useful. But it was interesting enough for curious people to study.\u201d\u00a0<\/p>\n<\/blockquote>\n
As of today, there are at least 18 clinical trials using base editing or prime editing to treat a range of diseases, with dozens of patients already treated, Liu said.<\/p>\n
Liu connects his research to basic science \u2014 research that seeks to understand something new about the world without a clear application in mind \u2014 that began at Japan\u2019s Osaka University in 1987. There, a team of researchers noticed something unusual in DNA from E. coli bacteria: highly repetitive DNA sequences that were interspersed with non-repetitive sequences, but with the exact same spacing. The phenomenon became known as Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR.<\/p>\n
\u201cThere was no knowledge of what CRISPR did, or whether it was going to be useful,\u201d Liu said. \u201cBut it was interesting enough for curious people to study. This is the essence of basic science.\u201d\u00a0<\/p>\n
Over the course of decades, researchers learned that CRISPR was a kind of immune system that bacteria use to protect themselves from viruses. When a virus enters a bacterial cell, the bacterium incorporates some of the virus\u2019s DNA as a kind of genetic memory, allowing it to identify and destroy the virus if it encounters it again.\u00a0<\/p>\n
\u201cYou can imagine a critic saying, \u2018Why do I care about a bacteria\u2019s ability to kill a virus?\u2019\u201d Liu said. \u201cThe answer is that it turned out to lead to all the CRISPR nuclease clinical trials, and eventually led to base editing and prime editing, and now we can make just about any kind of change in the DNA of living systems, including correcting the vast majority of mutations that lead to genetic disease. And it all came from the basic science of geneticists who first looked at these clustered regularly interspaced short palindromic repeats and wondered what they were doing.\u201d\u00a0<\/p>\n
Liu is loath to call his technologies a cure: \u201cScientists are reluctant to use that word until there\u2019s evidence of years without any apparent symptoms of the disease,\u201d he said. But, he added, \u201cThe writing\u2019s already on the wall: In some of these clinical trials, the patients are no longer on any medication and don\u2019t have any symptoms of the disease.\u201d<\/p>\n
Looking to the future of research and innovation, Liu says he\u2019s deeply worried about the current threat to the partnership between higher ed and the federal government, especially as it relates to young scientists.<\/p>\n
\u201cThere\u2019s a lot of fear and chaos now that is preventing young scientists from entering the phase of their careers where they can contribute to society in a direct way,\u201d he said. \u201cAnd that\u2019s a very real tragedy.\u201d<\/p>\n
\t\t\t\t\t\t\tMore like this<\/p>\n","protected":false},"excerpt":{"rendered":"In 2022, Alyssa Tapley was 13, suffering from T-cell leukemia, and facing a grim prognosis after existing treatments…\n","protected":false},"author":2,"featured_media":53454,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[267,3941,2343,28513,70,16,15],"class_list":{"0":"post-53453","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-health-care","10":"tag-research","11":"tag-research-powers-progress","12":"tag-science","13":"tag-uk","14":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114407163150241579","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/53453","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=53453"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/53453\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/53454"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=53453"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=53453"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=53453"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}