Quick questions on Future directions of genetic research: germline editing, gene drives and synthetic biology: HSC Biology Module 6

What it is. Editing DNA in eggs, sperm or embryos so the change is passed to all cells of the future person and to their descendants.

What it is. A CRISPR-based element that copies itself onto the homologous chromosome in every individual, so the drive is inherited by close to 100 percent of offspring instead of 50 percent. A drive can spread through a wild population in a few dozen generations.

Prime editing (2019). A "search and replace" CRISPR system that can write small new sequences into a chosen location without a double-strand break. Lower off-target rate than original CRISPR-Cas9. Approaching clinical trials for sickle cell and other monogenic diseases.

The COVID-19 mRNA vaccines (Pfizer-BioNTech, Moderna) proved the platform at scale. Future applications:

The engineering of new biological systems from standardised genetic parts.

Transplanting genetically modified animal organs into humans. Pigs engineered with CRISPR to remove pig-specific antigens and inactivate endogenous retroviruses (PERVs) have been used in two heart transplants (2022 and 2023) and several kidney transplants. The recipients all died within months but proved the technology works in principle. With ongoing organ shortages (about 1,800 Australians on the transplant waiting list at any time) the technology has significant potential.

WGS-guided treatment is moving from research into routine care. By the late 2020s, sequencing at birth is likely to be common in high-income countries, with pharmacogenomic dosing recommendations attached to every prescription.

DeepMind's AlphaFold (2020) solved the protein structure prediction problem. RFdiffusion and similar generative models design new proteins computationally. This accelerates drug discovery, enzyme engineering and vaccine design.

Editing DNA in eggs, sperm or embryos so the change is passed to all cells of the future person and to their descendants.

Technically possible since 2014 (CRISPR in mouse embryos) and demonstrated in humans by He Jiankui in 2018, who edited the CCR5 gene in twin embryos in an attempt to confer HIV resistance. He was prosecuted in China and the scientific community condemned the experiment as premature and unethical.

Prevention of severe inherited disease in families where preimplantation diagnosis cannot help (both parents homozygous for a recessive condition).

Banned or strictly limited in almost every jurisdiction; a global moratorium has been proposed by leading scientists.

Irreversibility, cross-border spread, ecosystem consequences, governance gap.

A "search and replace" CRISPR system that can write small new sequences into a chosen location without a double-strand break. Lower off-target rate than original CRISPR-Cas9. Approaching clinical trials for sickle cell and other monogenic diseases.

Converts one base directly to another (e.g. C to T) without cutting both strands. Verve Therapeutics has run trials for inherited hypercholesterolaemia.