Research

As a quote from Richard Feynman, "What I cannot create, I do not understand".

The design, manipulation, and synthesis of entire genomes provide a powerful strategy for studying basic biology and developing biotechnical applications. Understanding how genotypes control phenotypes has been one of the most fundamental aspects of biology. If granted the ability to robustly and accurately manipulate and synthesize a large genomic region, an entire chromosome, and ultimately an entire genome, we can potentially introduce genotypic perturbations into a living system at any arbitrary scale and ask the question: how do defined genomic modifications determine designed biological features? More daringly, how can we craft synthetic genomes to enable novel functions beyond the limits of nature? Once achieved, such novel "true genome-scale" writing and manipulating technologies have the potential to markedly accelerate or even to transform basic research and applications in a wide range of biological and biomedical areas including – but not limited to – genetic code reassignment, creation of novel chimeric life forms, understanding the essence of life with minimised genome, gene therapy, CAR T-cell immunotherapy, humanized animal models, xenotransplantation, and epigenetic studies.

However, the conventional DNA engineering techniques widely used today fall short of the demand of "true genome-scale" synthesis and manipulation. Standard molecular biology techniques such as restriction digestion, gel purification, ligation, Gibson Assembly, transformation, recombination developed in the 1980's to 2000's are designed to manipulate DNA of the size ranging from kilobases to 10's of kilobases. As a result, despite being sufficient to handle DNA at individual gene or gene cluster level, and paving the foundation to modern day life sciences, they are insufficient to enable true genome-scale modifications.

To answer this challenge, we aim to develop greater capacity in DNA manipulation, or another way of putting it, genome synthesis.