The CombiGEM-CRISPR Platform

Key research topic

High-throughput combinatorial genetics for discovery of effective combination regimens.

Challenges

previous
drugscreen
platform

Objectives

• Establish high-throughput combinatorial genetics platforms

• Enable rapid discovery of effective anti-cancer therapeutic combinations

• Enable identification of efficient cell differentiation protocols

Significance

Despite the enormous potential with combination therapy, there are only limited combination regimens that have been isolated and characterized. To circumvent the need to individually test every possible combinations that is prohibitively expensive and impracticable, our platform enable the rapid discovery of combination-based treatment strategies for various complex diseases, including devising combination drug therapies for cancers and new cell differentiation formulas involving specific combinatorial effectors important for regenerative medicine applications.

Main projects

• Establishment of combinatorial genetics platforms to enable high-throughput screening of combinations.

• High-throughput discovery of effective anti-cancer therapeutic combinations

• High-throughput discovery of efficient cell differentiation protocols

Recent results particularly on breakthroughs and milestones

Many disease pathogeneses are governed by multifactorial interactions between complex sets of genes and pathways, rather than contributed solely by a single genetic perturbation. Our platform under development can be readily applied to study other diseases for identifying novel mechanisms that point the way to new therapeutics, and we look forward to more collaborative efforts to broaden the translational impact of our platform technology.

Key members, partners and collaborators (Our team)

Alan S. L. Wong (PI)

Suet Yi Leung (Co-I)

Stephanie K.Y. Ma (Co-I)

Dong-yan Jin (Co-I)

Song-eng Cheah (Co-I)

pnas

Selected Publications

Wong, A. S., Choi, G. C., Cui, C. H., Pregernig, G., Milani, P., Adam, M., ... & Shalek, A. K. (2016). Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM. Proceedings of the National Academy of Sciences, 201517883.

[This study has been highlighted in:

¬ Research Highlights of Nature Reviews Genetics (http://www.nature.com/nrg/journal/vaop/ncurrent/full/nrg.2016.24.html)

¬ Highlights of the Issue, Proceedings of National Academy of Sciences (http://www.pnas.org/content/113/9/2319.full)

¬ Principles of Systems Biology – No. 6 of Cell Systems (Invited Commentary) (http://www.cell.com/cell-systems/pdf/S2405-4712(16)30187-9.pdf)

¬ Addgene blog (Invited) (http://blog.addgene.org/pairing-combigem-and-crispr-for-combinatorial-genetic-screening)

natbio

Wong, A. S., Choi, G. C., Cheng, A. A., Purcell, O., & Lu, T. K. (2015). Massively parallel high-order combinatorial genetics in human cells. Nature biotechnology, 33(9), 952.

[This study has been highlighted in:

¬ Research Highlights of Nature Reviews Genetics (http://www.nature.com/nrg/journal/vaop/ncurrent/full/nrg4008.html)