How important is it that cell and nucleus remain intact for your application? Can other chromosomes be genetically engineered? What will happen to the chromosome once identified? Do you need to be able to identify chromosomes during M phase, or is interphase OK? How many chromosomes do you need to identify and extract?
For cell-culturing methods, we want the cell intact and alive. In this context, identification is less of a problem, because you can always do selection after the fact. See https://en.wikipedia.org/wiki/Microcell-mediated_chromosome_transfer ; it’s fine if many of your microcells contain the wrong chromosome and then you transmit the wrong chromosome, because you can select in your cell culture after doing the trasmission. See e.g. Petris, Gianluca, Simona Grazioli, Linda van Bijsterveldt, et al. ‘High-Fidelity Human Chromosome Transfer and Elimination’. Science 390, no. 6777 (2025): 1038–43. https://doi.org/10.1126/science.adv9797
Do you need to be able to identify chromosomes during M phase, or is interphase OK?
For isolating-ensembling methods, we’re presumably destroying the cell and nuclear membrane, and dissociating the nucleus. Since we’re handling naked chromosomes, we want them to be M-phase or otherwise compact (e.g. sperm chromatin). Interphase is probably too spread out and too vulnerable; the chromosomes would likely literally break.. Though I’m not 100% sure of that.
How many chromosomes do you need to identify and extract?
If it’s a cell-culture method, you could do any number. The more you can do, the better, because that means more selection power (i.e. more ability to vector traits of the resulting kid).
If it’s an isolating-ensembling method, then you must produce either a full euploid haploid or a full euploid diploid genome, depending on context (e.g. are you making a paternal genome or a zygote genome). So you have to do 23 or 46 chromosomes. (You don’t necessarily have to do them each individually, as singletons; see https://berkeleygenomics.org/articles/Chromosome_identification_methods.html#setwise-identification )
How important is it that cell and nucleus remain intact for your application? Can other chromosomes be genetically engineered? What will happen to the chromosome once identified? Do you need to be able to identify chromosomes during M phase, or is interphase OK? How many chromosomes do you need to identify and extract?
There’s a dichotomy in chromosome selection methods, where either you’re manipulating chromosomes a bunch while they’re still in cells, or else you’re extracting them and manipulating them individually. See https://berkeleygenomics.org/articles/Chromosome_identification_methods.html#cell-culturing-vs.-isolating-ensembling-methods . For reasons mentioned there, I’m inclined towards isolating-ensembling methods.
For cell-culturing methods, we want the cell intact and alive. In this context, identification is less of a problem, because you can always do selection after the fact. See https://en.wikipedia.org/wiki/Microcell-mediated_chromosome_transfer ; it’s fine if many of your microcells contain the wrong chromosome and then you transmit the wrong chromosome, because you can select in your cell culture after doing the trasmission. See e.g. Petris, Gianluca, Simona Grazioli, Linda van Bijsterveldt, et al. ‘High-Fidelity Human Chromosome Transfer and Elimination’. Science 390, no. 6777 (2025): 1038–43. https://doi.org/10.1126/science.adv9797
Not sure what you mean. You’re asking, do we create chromosomes, e.g. via CRISPR editing? We could, but that’s not necessary. You could get quite a lot of mileage just selecting from easily-obtainable ordinary cells. See https://berkeleygenomics.org/articles/Methods_for_strong_human_germline_engineering.html#method-chromosome-selection
For isolating-ensembling methods, we’re presumably destroying the cell and nuclear membrane, and dissociating the nucleus. Since we’re handling naked chromosomes, we want them to be M-phase or otherwise compact (e.g. sperm chromatin). Interphase is probably too spread out and too vulnerable; the chromosomes would likely literally break.. Though I’m not 100% sure of that.
If it’s a cell-culture method, you could do any number. The more you can do, the better, because that means more selection power (i.e. more ability to vector traits of the resulting kid).
If it’s an isolating-ensembling method, then you must produce either a full euploid haploid or a full euploid diploid genome, depending on context (e.g. are you making a paternal genome or a zygote genome). So you have to do 23 or 46 chromosomes. (You don’t necessarily have to do them each individually, as singletons; see https://berkeleygenomics.org/articles/Chromosome_identification_methods.html#setwise-identification )