2
$\begingroup$

Jennifer Doudna mentioned in https://youtu.be/9Yblg9wDHZA?t=2566 on 2019-02-21 that He Jiankui introduced an unseen variant of the CCR5 gene when gene editing the twin humans Lulu and Nana. What advantage might there be for using that unseen variant instead of the naturally occurring CCR5-∆ 32 mutation?

Figure from the above-mentioned YouTube presentation showing the CCR5 gene and some variants:

enter image description here


I have crossposted the question at:

$\endgroup$
  • $\begingroup$ Interesting question, but this seems very opinion based and speculative — I suggested some edits to try to overcome this, but they may not pass muster ... $\endgroup$ – tyersome Jul 7 at 3:05
  • $\begingroup$ @tyersome Thanks for the edit! Understanding the impact of gene mutations on the phenotype is an important scientific question, and I assume that He Jiankui has some scientific grounding for his choice. $\endgroup$ – Franck Dernoncourt Jul 7 at 3:09
  • $\begingroup$ You're welcome! He likely thought he had good reasons, but considering how poorly thought out his experiment seems to have been I wouldn't count on it! $\endgroup$ – tyersome Jul 7 at 3:19
  • $\begingroup$ @tyersome George Church, who reviewed He Jiankui's 2 papers regarding this experiment, mentioned that it seems to have been carried out quite meticulously (put aside the ethical discussion). E.g., the genome was sequenced a few times after the edit to ensure that the edit went as expected. $\endgroup$ – Franck Dernoncourt Jul 7 at 3:27
  • $\begingroup$ I don't think we can put aside the ethical issues or even completely separate them from the technical. For example my understanding is that mutation of CCR5 may put the girls at increased risk of other diseases including: Breast cancer — ascopubs.org/doi/abs/10.1200/jco.2015.33.28_suppl.17; Immune system hyperactivity — ncbi.nlm.nih.gov/pubmed/23250822. $\endgroup$ – tyersome Jul 7 at 4:48
2
$\begingroup$

Possibly He Jiankui was using Cas9 without a template DNA. If so, this generates double-stranded breaks that are repaired through processes such as non-homologous end joining (NHEJ) that often produce small indels (deletions and insertions) 1.

This is consistent with the apparently random small deletions and insertions around the cut site seen in both girls.

An additional, unflattering possibility is that this way he could prove that these were his edits and didn't happen spontaneously.

Useful starting points for understanding how Cas9 works can be found at the Addgene website and on Wikipedia.


Reference:

1: Brinkman, Eva K et al. “Kinetics and Fidelity of the Repair of Cas9-Induced Double-Strand DNA Breaks.” Molecular cell vol. 70,5 (2018): 801-813.e6. doi:10.1016/j.molcel.2018.04.016

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.