4 ms·

Alternative CRISPR system could improve genome editing

44 points by etiam 11y ago

tomkinstinch 11y ago
From the Broad's press release, on how the new system is different[1]: "The newly described Cpf1 system differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics, as well as for business and intellectual property: First: In its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues. Second, and perhaps most significantly: Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving ‘blunt ends’ that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately. Third: Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur. Fourth: the Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting some genomes, such as in the malaria parasite as well as in humans." 1. https://www.broadinstitute.org/news/7272 https://www.broadinstitute.org/news/7272
benchtobedside 11y ago
Can anyone comment on how this may impact the IP landscape for CRISPR? [0] [0] http://www.the-scientist.com/?articles.view/articleNo/42595/title/Who-Owns-CRISPR-/ http://www.the-scientist.com/?articles.view/articleNo/42595/...
- dekhn 11y ago
  Zero impact on CRISPR IP except that if it really does have the properties they're claiming, I don't think people will even use CRISPR.
  - dekhn 11y ago
    Minor correction. The new system is a form of CRISPR. The impact would be on Cas9 IP.
- josaka 11y ago
  Zhang's patent US 8,697,359 is limited to techniques in which "the Cas9 protein cleaves the DNA molecule." If this new technique does not use the Cas9 protein in this fashion, it would potentially provide a design-around, meaning that the benefit of the patented idea can be obtained without infringing the patent. New patents may have issued that are not so limited.
  - benchtobedside 11y ago
    Thanks for clarifying. Further to this comment from [0]: "But with Cfp1, the stakes of that specific patent dispute go down. A lab or company could use Cfp1 without infringing on the CRISPR/Cas9 patent. " [0] http://www.wired.com/2015/09/war-genome-editing-just-got-lot-interesting/?mbid=social_twitter http://www.wired.com/2015/09/war-genome-editing-just-got-lot...

44 points by etiam 11y ago

From the Broad's press release, on how the new system is different[1]: "The newly described Cpf1 system differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics, as well as for business and intellectual property: First: In its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues. Second, and perhaps most significantly: Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving ‘blunt ends’ that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately. Third: Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur. Fourth: the Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting some genomes, such as in the malaria parasite as well as in humans." 1. https://www.broadinstitute.org/news/7272 https://www.broadinstitute.org/news/7272

benchtobedside 11y ago

Can anyone comment on how this may impact the IP landscape for CRISPR? [0] [0] http://www.the-scientist.com/?articles.view/articleNo/42595/title/Who-Owns-CRISPR-/ http://www.the-scientist.com/?articles.view/articleNo/42595/...

dekhn 11y ago
Zero impact on CRISPR IP except that if it really does have the properties they're claiming, I don't think people will even use CRISPR.
- dekhn 11y ago
  Minor correction. The new system is a form of CRISPR. The impact would be on Cas9 IP.
josaka 11y ago
Zhang's patent US 8,697,359 is limited to techniques in which "the Cas9 protein cleaves the DNA molecule." If this new technique does not use the Cas9 protein in this fashion, it would potentially provide a design-around, meaning that the benefit of the patented idea can be obtained without infringing the patent. New patents may have issued that are not so limited.
- benchtobedside 11y ago
  Thanks for clarifying. Further to this comment from [0]: "But with Cfp1, the stakes of that specific patent dispute go down. A lab or company could use Cfp1 without infringing on the CRISPR/Cas9 patent. " [0] http://www.wired.com/2015/09/war-genome-editing-just-got-lot-interesting/?mbid=social_twitter http://www.wired.com/2015/09/war-genome-editing-just-got-lot...