Genome complexity: Explaining Crispr (Introduction)

by David Turell , Saturday, October 22, 2016, 19:13 (2742 days ago) @ David Turell

Bacteria contain enzymes to protect themselves from attack. These enzymes are giant molecules modified and used in research labs to study DNA by breaking it up an reinserting genes:

http://www.wsj.com/articles/a-genetic-chain-saw-to-target-harmful-dna-1477081818

Many people are excited by the potential of the genetic tool Crispr-Cas9 to serve as a kind of molecular scissors to cut and repair malfunctioning DNA.

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"Crispr, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is thought to have evolved in bacteria over millions of years. Crispr is the immune system of the bacteria, capturing an invader’s DNA and integrating it into the genome of the bacteria to fend off future attacks.

"Several years ago, scientists demonstrated a way to reprogram an enzyme called Cas9 in the Crispr system to enable the editing of genes—opening up the potential to someday cure genetic diseases.

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"There are actually six major types of Crispr systems in nature, each of which uses different enzymes to perform tasks. Dr. Barrangou wants to use the Crispr-Cas3 system to take on antibiotic resistance.

"The Cas9 and Cas3 enzymes have some things in common. For one thing, both can be programmed to target DNA. But Cas9 cuts DNA like a surgeon’s scalpel, causing a break that can then be repaired. Cas3, says Dr. Barrangou, operates more like Pac-Man, chewing up DNA and causing extensive damage that can’t be readily fixed. Dr. Barrangou says that the goal is to get harmful bacteria to commit cell suicide.

“'Cas3 is a meaner system and more cumbersome than Cas9,” he says. “But if you want to cut a tree and get rid of it, you bring a chain saw, not a scalpel.”
Dr. Barrangou and his colleagues founded a company called Locus Biosciences in Raleigh, N.C., to use reprogrammed Crispr-Cas3 to develop antimicrobials and tackle infectious diseases that are increasingly resistant to antibiotics, such as C.difficile, E.coli and MRSA. Challenges remain, including testing the delivery of Crispr to the bacteria. “We aren’t trying to edit it,” says Paul Garofolo, Locus’s CEO. “We are trying to kill it.”

"This new focus on the potential of other Crispr systems can be traced at least in part, scientists say, to a 2015 study in the journal Cell identifying a new system called Cpf1 that cuts differently than Cas9. Researchers contend that Cpf1 may ultimately allow for more precise gene editing in humans than Cas9.

Comment: Note these are man-made modifications of bacterial defense enzymes. What is always striking to me is that bacteria in evolving these huge molecules had to invent them. Enzymes are giant in size and have loci which will grab both sides of a reaction, hold the molecules together and force a reaction that would otherwise take years to occur. Chance logically cannot create this. Saltation is logical.