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Currently Skimming:

Genome Editing with Precision and Accuracy - Krishanu Saha
Pages 27-34

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From page 27...
... New genome editing tools are now capable of "one in a billion" specificity, leading to the prospect of new classes of gene and cell therapies. To illustrate both the excitement and the risks, I begin with a cautionary tale that made global headlines, before describing opportunities and challenges in efforts to develop genome ­ ditors for biomedical applications.
From page 28...
... . CHALLENGE 1: ON-TARGET NUCLEASE ACTIVITY The most common interpretation of "precision" in genome editing is the ability to edit the genome at the intended target site while limiting edits elsewhere in the genome, commonly called "off-target effects." For the CRISPR-Cas9 genome editing systems, Cas9 has been observed to create excessive undesirable mutations (Cradick et al.
From page 29...
... The protoadjacent motif in the host genome used by Cas proteins for target recognition are shaded in blue; the DNA sequence in the host genome bound by the genome editor is in green at the intended (on-target) locus and in red at the unintended (off-target)
From page 30...
... . CHALLENGE 3: PRECISE TRANSCRIPTIONAL CONTROL Even if challenges 1 and 2 are met with perfect accuracy and precision, expression of edited genes to generate RNA transcripts can vary over time as well as across cell differentiation and behavior patterns.
From page 31...
... CHALLENGE 4: PRECISE EDITING IN SPECIFIC CELLS AND TISSUES Precise delivery of editing components to the right cells and tissues remains a challenge as many delivery agents suffer from low efficiency, high toxicity, and immuno­ enicity, but viral and nonviral delivery agents have been engineered to g achieve cell and tissue specificity. Viral constructs can be engineered to harbor cell- and tissue-specific promoters that drive expression of the gene editing system (Ran et al.
From page 32...
... :490–95. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR.
From page 33...
... :142–47. Zuris JA, Thompson DB, Shu Y, Guilinger JP, Bessen JL, Hu JH, Maeder ML, Joung JK, Chen Z-Y, Liu DR.


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