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January 7 - January 18, 2019
the genome—an organism’s entire DNA content, including all its genes—has become almost as editable as a simple piece of text.
The CRISPR technology is so simple and efficient that scientists could exploit it to modify the human germline—the stream of genetic information connecting one generation to the next. And, have no doubt, this technology will—someday, somewhere—be used to change the genome of our own species in ways that are heritable, forever altering the genetic composition of humankind.
A global discussion about gene editing has already begun; it’s a historic debate about nothing less than the future of our world. The wave is coming. Let’s paddle out and ride it together.
Interestingly, a genome’s size is not an accurate predictor of an organism’s complexity; the human genome is roughly the same length as a mouse or frog genome, about ten times smaller than the salamander genome, and more than one hundred times smaller than some plant genomes.
A full 8 percent of the human genome—over 250 million letters of DNA—is a remnant of ancient retroviruses that infected ancestors of our species millennia ago.
Finally, the words that the acronym stood for—clustered regularly interspaced short palindromic repeats—began to make sense to me. The diamonds were the short repeats, the squares were interspacing sequences that regularly interrupted the repeats, and these diamond-square arrays were clustered in just one region of the chromosome, not randomly distributed throughout.
In 1977, Fred Sanger and his colleagues succeeded in determining the complete DNA genome sequence of a phage called ΦX174. Twenty-five years later, the same phage would again become famous: its genome was the first to be synthesized entirely from scratch.
CRISPR-associated genes, or cas genes,
Out of this fifth bacterial weapons system, we had built the means to rewrite the code of life.
By combining all these molecular parts, Martin and I intended to convert human cells into CRISPR-producing factories that unwittingly churned out molecules programmed to target and cut up their own genome.
if CRISPR succeeded in cutting a gene, the cell would respond by simply gluing the DNA back together, much like welding two pieces of metal pipe together. Scientists refer to this process as nonhomologous end joining, since, unlike homologous recombination, the mending does not involve a matching repair template.
In what felt like no time at all, CRISPR had already caught up to almost twenty years of research and development in other gene-editing technologies.
Science magazine, which had published our previous CRISPR paper just six months prior, named genome editing one of the runner-up breakthroughs of the year (first prize went to the Higgs boson) but highlighted an older technology—TALEN—that had been discovered just before our work with CRISPR.
Moreover, they showed that CRISPR could be programmed with not just one RNA guide, but multiple different guides, directing Cas9 to cut up and edit several DNA sequences in mouse embryos simultaneously. This
But with CRISPR, gene editing was now so powerful and multifaceted that it was often referred to as genome engineering, a reflection of the supreme mastery that scientists held over genetic material inside living cells.
As I explained to the class, CRISPR can be described as a pair of designer molecular scissors because of its core function: to home in on specific twenty-letter DNA sequences and cut apart both strands of the double helix.
The simplest use of CRISPR is also the one that’s most widely employed: have it cut a specific gene and then allow the cell to repair the damage by reconnecting the strands.
