Question

Here's a silly idea I had this morning:

Sequence a bunch of normal patient cells.
Sequence a bunch of tumor cells from a biopsy.
Find a DNA sequence that we're reasonably certain exists in the cancer cells but doesn't exist in normal cells.
Create a guide DNA that matches the sequence identified in (3).
Send in a nuclease dead cas9 which stops cell replication through an AAV to all the cells anywhere in the vicinity of the tumour. It specifically binds only to the DNA in the cancer cells, and therefore disables DNA replication only for those cells. Then, target the now-stagnant tumour using conventional chemotherapy.
Alternatively, send in a CRISPR dead cas that induces apoptosis upon binding to the target strand, though this seems harder to pull off.
Would something like this work? If so, has this been attempted? If not, what specific step is impossible?

Answer 1

Using CRISPR/Cas9 technology for cancer treatment by targeting unique DNA sequences in cancer cells is an innovative approach and technically possible. It involves sequencing DNA, engineering sgRNAs, and employing nuclease-dead Cas9. However, this method is still under research and faces challenges such as specificity, delivery, and expression in vivo.

Step-by-step explanation:

Feasibility of Targeted CRISPR/Cas Systems for Cancer Treatment

The idea of using CRISPR/Cas9 technology to target cancer cells by identifying exclusive cancer cell DNA signatures and then using a guide RNA (gRNA) to deliver nuclease-dead Cas9 is intriguing and innovative. Essentially, the process would involve sequencing normal and cancer cell DNA, identifying unique sequences present only in cancer cells, and engineering an sgRNA to target these sequences. The nuclease-dead Cas9, once delivered, would block DNA replication or induce apoptosis in these cells.

There are multiple steps involved in this potential cancer treatment, some of which pose scientific challenges. The CRISPR system has been adapted to gene editing needs by creating sgRNAs targeting specific sites in chromosomal DNA. Once inserted into a plasmid, the CRISPR/Cas9 complex can locate the gene in question but, with the nuclease activity disabled, it only blocks transcription, not excises the DNA. This method, known as CRISPR interference (CRISPRi), can be used to silence any gene, including those in cancer cells.

While the process seems theoretically possible and has been somewhat attempted in research settings, there are challenges to ensure specificity and efficacy in targeting only cancer cells while preventing off-target effects. Moreover, efficient delivery and sustained expression of the CRISPR/Cas9 components in vivo need to be optimized. While not impractical, such therapeutic interventions would require extensive research and testing to become a reality for treating patients.