CRISPR and unwanted DNA alterations

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In summary, the conversation discusses the potential dangers of using CRISPR-Cas9 as a gene editing tool. Recent studies have shown that this technology can lead to large deletions and complex rearrangements in DNA, which could have negative consequences for patients. However, the scope of the study is limited to cell lines and mice, and the long-term effects on humans are still unknown. While there is some concern about the potential risks, some argue that unexpected outcomes in experiments can also lead to positive results.
  • #1

jim mcnamara

@Ygggdrasil is far more qualified to comment on this than I am, but it seems like a good idea to raise the issue. Published today July 16, 2018 Letter in Nature Biotechnology:
M. Kosicki, K. Tomberg & A Bradley
Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex
CRISPR–Cas9 is poised to become the gene editing tool of choice in clinical contexts. Thus far, exploration of Cas9-induced genetic alterations has been limited to the immediate vicinity of the target site and distal off-target sequences, leading to the conclusion that CRISPR–Cas9 was reasonably specific. Here we report significant on-target mutagenesis, such as large deletions and more complex genomic rearrangements at the targeted sites in mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line. Using long-read sequencing and long-range PCR genotyping, we show that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases. Furthermore, lesions distal to the cut site and crossover events were identified. The observed genomic damage in mitotically active cells caused by CRISPR–Cas9 editing may have pathogenic consequences.

In plain English this says that DNA gets changed by CRISPR as presented before. It also changes DNA in places/ways that were not intended. This was tested only on cell lines (not people) and some mice.
Obviously a bad change in a human patient has a probability to cause problems for the patient. However I do not understand the scope of the report. For example, most kinds of medical treatments carry risk. So is this article "hype" or reasonable? Clearly, somebody thought it had some merit to be published at

Insight article on the CRISPR -']crispr-new-gene-editing-technologies-wont-lead-designer-babies/[/URL]
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  • #2
From an information-theoretic standpoint, "DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases", seems rather foreboding.
  • #4
The problem is we have no idea, we are experimenting, getting results that are not expected and have no clue what the end result will be. That said..many good things have resulted from unexpected outcomes of experiments. Push on.!

What is CRISPR and how does it work?

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and it is a gene-editing tool that allows scientists to make precise changes to an organism's DNA. It works by using a protein called Cas9 to target and cut specific sections of DNA, which can then be replaced with desired sequences.

What are unintended DNA alterations and how do they occur in CRISPR?

Unintended DNA alterations, also known as off-target effects, occur when the CRISPR system mistakenly cuts and edits DNA sequences that were not intended to be altered. This can happen due to similarities in DNA sequences or other factors that cause Cas9 to target the wrong location.

What are the potential risks and ethical concerns of using CRISPR?

There are several potential risks associated with using CRISPR, such as unintended DNA alterations and the potential for long-term effects on an organism's health. Ethical concerns also arise regarding the use of CRISPR in altering human DNA and the implications of making permanent changes to the genetic code.

How can scientists reduce the risk of unintended DNA alterations when using CRISPR?

Scientists can reduce the risk of off-target effects by carefully designing and selecting target DNA sequences, using more accurate versions of Cas9, and performing thorough testing and analysis of the edited DNA. Additionally, new technologies are being developed to improve the precision of CRISPR editing.

What are the potential applications of CRISPR and unwanted DNA alterations in research and medicine?

CRISPR has the potential to revolutionize the fields of research and medicine by allowing scientists to make precise edits to DNA sequences and study the effects of these changes. It can also be used in gene therapy to treat genetic diseases and potentially cure them by correcting the underlying genetic mutations.

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