Can we change the Eye/Hair color by knocking out the OCA2, HERC2 and MC1R genes using CRISPR in an adult human?

Question

This paper seems to describe the use of a plasmid delivered by a gene gun to depigment rat skin;

https://www.nature.com/articles/3302264 Published: 27 May 2004 Seeing the gene therapy: application of gene gun technique to transfect and decolour pigmented rat skin with human agouti signalling protein cDNA

Could a similar technique using CRISPR and chitosan change the eye and hair color of an an adult?

Answer 1

Let's first breakdown this question

What is CRISPR?

• CRISPR is a group of DNA sequences that play a key role in the antiviral defense system of prokaryotic organisms such as bacteria and archaea.
• They are derived from DNA fragments of bacteriophages that had previously infected the prokaryotes.
• These sequences are used to destroy DNA from similar bacteriophages for future infections.

What is CRISPR-Cas?

• The CRISPR-Cas system is an immune system seen in prokaryotes that provides resistance to foreign elements such as plasmids and phages. This is a form of acquired immunity.
• Some factors allow Cas protein which is an enzyme to recognize and cut foreign pathogenic DNA making them act like a pair of molecular scissors.

What are OCA2, HERC2, and MC1R?

Now we know we can cut a specific part (Gene) of DNA. What do we accomplish by cutting out the genes which Andrew mentioned? To answer this we need to know what those three genes do.

1. OCA2 (P-gene): Provides instructions for making a protein called the P protein. This protein is located in specialized cells (melanocytes) that produce a pigment called Melanin. Melanin is a natural skin pigment. Hair, skin, and eye color in people and animals mostly depends on the type and amount of melanin they have.
2. HERC2 (E3 ubiquitin ligase HERC2): Protein ligase which helps in DNA repair regulation, pigmentation, and neurological disorders.
3. MC1R (Melanocortin 1 receptor): Proteins involved in regulating mammalian skin and hair color.

In short, these Genes affect the Eye and Hair Colour and Andrew is suggesting to us that by removing/modifying them using CRISPR we change the Eye/Hair Colours.

Can we knock out OCA2, HERC2, and MC1R?

Yes, it has been done before and there are sequences available to target these genes within the genome. An example would be the gRNA sequences developed by Sigma-Aldrich and Genscript. I'll provide links of articles which has knocked out the respective gene and links to the gene sequences.

• OCA2: (Article: https://pubmed.ncbi.nlm.nih.gov/29555241/ | Sequence: https://www.genscript.com/gRNA-detail/4948/OCA2-CRISPR-guide-RNA.html)
  
• HERC2: (Article: https://jmg.bmj.com/content/early/2020/06/22/jmedgenet-2020-106873 | Sequence: https://www.sigmaaldrich.com/catalog/genes/HERC2)
  
• MC1R: (Article: https://www.genscript.com/gRNA-detail/4157/MC1R-CRISPR-guide-RNA.html | Sequence: https://www.genscript.com/gRNA-detail/4157/MC1R-CRISPR-guide-RNA.html)
  

Can we change the Eye/Hair Colour by modifying the above genes?

An Interesting article from MIT Technology Review called Engineering the Perfect Baby gives you a nice idea of what I am going to tell you.

In Theory: It's technically possible. We can put up a convincing theory and there is a huge chance that this can be successfully done.

In Reality: Well, Reality kinda sucks cause most of the genetic engineering breakthrough starts from failures. Killing a rat for scientific purposes won't make any big difference but what about killing a fetus? It's almost impossible to get the permissions required to use CRISPR to edit the human genome even if it is to find a cure for a deadly disease that would actually improve the human race significantly. Due to its obvious ethical questions, people always stand against it. I said "almost impossible" cause there are few people who actually got the permissions and there are indeed few ongoing trials experimenting with CRISPR on Human Genome.

A popular Example would be He Jiankui who gave rise to the first-ever gene-modified human babies "Lulu and Nana". He had to forged ethical review documents, misled doctors into unknowingly implanting gene-edited embryos into two women, and many more things which haven't come out yet. What are the consequences? He's bloody missing! May 2022 Update: He's been found.

The point is, there is absolutely no way they would approve the usage of CRISPR for modifying something as silly as Eye/Hair color.

I mean we all like our babies to look like Megan Fox but I totally doubt if anyone would dare to modify a human genome for changing mere appearance cause people would start protesting if they find out someone is putting all those innocent fetuses at unknown and uncalculatable risk for changing external traits.

We want people to use CRISPR for things like this - Scientists edit gene for blood disease in human embryos and not for things like this - The rise of the designer baby: Parents who paid $16,500 to choose the sex of their child.

TL;DR (Too Long; Didn't Read):

What is CRISPR-Cas?

Technique in which we can edit genes relatively more precise than before.

What are OCA2, HERC2, and MC1R?

Genes which control the color of Eyes, Hair, Skin, and has other purposes.

Can we remove OCA2, HERC2, and MC1R genes using CRISPR?

Yes

Has it been done before?

Yes

In Humans?

Nope cause we got all those ethics and stuff.

What are we trying to accomplish by removing those genes?

To change the Colour of the Eyes/Hair of a human being.

Can we change the Colour of the Eyes/Hair of a human being?

In theory, it'll work. In Reality, nobody would allow it. They'd be better off with Hair Dye and Contact Lenses than to risk the lives of innocent fetuses.