Researchers are developing a CRISPR–Cas9 therapy to correct
a pathogenic point mutation in a gene responsible for an inherited blood
disorder. During preclinical testing, several unintended genomic regions are
also cleaved, raising concerns about off-target effects. The research team
decides to redesign part of the CRISPR system to improve targeting precision.

Which component of the CRISPR–Cas9 system would most
directly need to be modified to improve DNA targeting specificity, and why?

Question

Researchers are developing a CRISPR–Cas9 therapy to correct
a pathogenic point mutation in a gene responsible for an inherited blood
disorder. During preclinical testing, several unintended genomic regions are
also cleaved, raising concerns about off-target effects. The research team
decides to redesign part of the CRISPR system to improve targeting precision.

Which component of the CRISPR–Cas9 system would most
directly need to be modified to improve DNA targeting specificity, and why?

Accepted Answer

The
guide RNA, because it determines target recognition through complementary base
pairing with the DNA sequence

Answer

The
DNA repair machinery, because it determines where Cas9 introduces double-strand
breaks

Answer

The
Cas9 nuclease, because it directs CRISPR components to specific cell types

Answer

The
Cas9 nuclease, because it directly cleaves DNA through sequence-specific
recognition

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Researchers are developing a CRISPR–Cas9 therapy to correct a pathogenic point ...

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