full transcript

From the Ted Talk by David R. Liu: Can we cure genetic diseases by rewriting DNA?

Unscramble the Blue Letters

We realized that we could brroow, once again, the targeting mechanism of CRISPR scissors to bring the new base editor to the right site in a genome. But we quickly encountered an idnlerbice problem; namely, there is no protein that's known to convert A into G or T into C in DNA. Faced with such a serious stumbling block, most students would probably look for another project, if not another research advisor. (lhaeugtr) But Nicole agreed to proceed with a plan that seemed wllidy abotuimis at the time. Given the absence of a naturally occurring protein that performs the necessary chemistry, we deeidcd we would evolve our own protein in the laboratory to convert A into a base that behaves like G, starting from a protein that performs related chemistry on RNA. We set up a Darwinian survival-of-the-fittest soecilten seystm that explored tens of millions of pitoern variants and only allowed those rare variants that could perform the necessary chemistry to survive. We ended up with a protein shown here, the first that can convert A in DNA into a base that rbemeesls G. And when we attached that protein to the disabled CRISPR scosisrs, shown in blue, we produced the second base editor, which converts As into Gs, and then uses the same strand-nicking strategy that we used in the first base editor to trick the cell into rpinelacg the nonedited T with a C as it remakes that nkceid sartnd, thereby completing the conversion of an A-T base pair to a G-C base pair.

Open Cloze

We realized that we could ______, once again, the targeting mechanism of CRISPR scissors to bring the new base editor to the right site in a genome. But we quickly encountered an __________ problem; namely, there is no protein that's known to convert A into G or T into C in DNA. Faced with such a serious stumbling block, most students would probably look for another project, if not another research advisor. (________) But Nicole agreed to proceed with a plan that seemed ______ _________ at the time. Given the absence of a naturally occurring protein that performs the necessary chemistry, we _______ we would evolve our own protein in the laboratory to convert A into a base that behaves like G, starting from a protein that performs related chemistry on RNA. We set up a Darwinian survival-of-the-fittest _________ ______ that explored tens of millions of _______ variants and only allowed those rare variants that could perform the necessary chemistry to survive. We ended up with a protein shown here, the first that can convert A in DNA into a base that _________ G. And when we attached that protein to the disabled CRISPR ________, shown in blue, we produced the second base editor, which converts As into Gs, and then uses the same strand-nicking strategy that we used in the first base editor to trick the cell into _________ the nonedited T with a C as it remakes that ______ ______, thereby completing the conversion of an A-T base pair to a G-C base pair.

Solution

  1. incredible
  2. strand
  3. decided
  4. nicked
  5. protein
  6. selection
  7. resembles
  8. scissors
  9. ambitious
  10. borrow
  11. laughter
  12. wildly
  13. replacing
  14. system

Original Text

We realized that we could borrow, once again, the targeting mechanism of CRISPR scissors to bring the new base editor to the right site in a genome. But we quickly encountered an incredible problem; namely, there is no protein that's known to convert A into G or T into C in DNA. Faced with such a serious stumbling block, most students would probably look for another project, if not another research advisor. (Laughter) But Nicole agreed to proceed with a plan that seemed wildly ambitious at the time. Given the absence of a naturally occurring protein that performs the necessary chemistry, we decided we would evolve our own protein in the laboratory to convert A into a base that behaves like G, starting from a protein that performs related chemistry on RNA. We set up a Darwinian survival-of-the-fittest selection system that explored tens of millions of protein variants and only allowed those rare variants that could perform the necessary chemistry to survive. We ended up with a protein shown here, the first that can convert A in DNA into a base that resembles G. And when we attached that protein to the disabled CRISPR scissors, shown in blue, we produced the second base editor, which converts As into Gs, and then uses the same strand-nicking strategy that we used in the first base editor to trick the cell into replacing the nonedited T with a C as it remakes that nicked strand, thereby completing the conversion of an A-T base pair to a G-C base pair.

Frequently Occurring Word Combinations

ngrams of length 2

collocation frequency
base editors 13
point mutations 8
base pair 8
base editing 7
genetic diseases 6
dna sequence 4
crispr scissors 4
dna sequences 4
human genetic 4
molecular machines 4
base editor 4
sickle cell 3
cell anemia 3
important gift 2
billion letters 2
point mutation 2
hemoglobin gene 2
correct point 2
billion years 2
defense mechanism 2
double helix 2
viral dna 2
cut dna 2
naturally occurring 2
dna letter 2
dna base 2
disabled crispr 2
protein shown 2
post doc 2
pathogenic point 2

ngrams of length 3

collocation frequency
sickle cell anemia 3
human genetic diseases 3
correct point mutations 2

Important Words

  1. absence
  2. advisor
  3. agreed
  4. allowed
  5. ambitious
  6. attached
  7. base
  8. behaves
  9. block
  10. blue
  11. borrow
  12. bring
  13. cell
  14. chemistry
  15. completing
  16. conversion
  17. convert
  18. converts
  19. crispr
  20. darwinian
  21. decided
  22. disabled
  23. dna
  24. editor
  25. encountered
  26. ended
  27. evolve
  28. explored
  29. faced
  30. genome
  31. gs
  32. incredible
  33. laboratory
  34. laughter
  35. mechanism
  36. millions
  37. naturally
  38. nicked
  39. nicole
  40. nonedited
  41. occurring
  42. pair
  43. perform
  44. performs
  45. plan
  46. proceed
  47. produced
  48. project
  49. protein
  50. quickly
  51. rare
  52. realized
  53. related
  54. remakes
  55. replacing
  56. research
  57. resembles
  58. rna
  59. scissors
  60. selection
  61. set
  62. shown
  63. site
  64. starting
  65. strand
  66. strategy
  67. students
  68. stumbling
  69. survive
  70. system
  71. targeting
  72. tens
  73. time
  74. trick
  75. variants
  76. wildly