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Delivery of DNA Encoded Libraries (DELs) Intracellularly via Mechanoporation

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Who this is for:

  • Drug discovery groups and CROs

Opportunities

  • Direct to Biology DELs: Intracellular delivery to live cells enables target proteins to be in their native cellular context and drive desired phenotypes
  • More relevant hits: Higher probability that identified hits will continue to bind target in the desired cellular context

Results Obtained

  • Delivery of fluorescently tagged DEL libraries to iPSCs and HeLa cells
  • Verification that delivery does not cause bias and delivers the full diversity of compounds into cells

How We Did It

Portal uses mechanoporation to deliver virtually any cargo to diverse cell types while maintaining cell health. This enables intracellular delivery of impermeable molecules without the complications of electroporation or other delivery methods. Learn more about mechanoporation here! 

Robust DNA Encoded Library Delivery in iPSCs and HeLa Cells

iPSCs and HeLa’s were boosted with a fluorescently-tagged DNA encoded library (DEL) probe. Strong delivery efficiency was shown when measured using flow cytometry.


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Fig 1: Induced pluripotent stem cells (iPSCs) were mechanoporated with a fluorescently-tagged DNA encoded library (DEL) probe. Delivery efficiency was measured using flow cytometry to detect the fluorescent tag immediately after boosting. 

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Fig 2: HeLa cells were mechanoporated with a fluorescently-tagged DNA encoded library (DEL) probe. Delivery efficiency was measured using flow cytometry to detect the fluorescent tag immediately after boosting. 

DEL Delivered Proportionally into PBMCs with Mechanoporation

PBMCs were mechanoporated in the presence of a diverse DEL. After washing, the cells were lysed and analyzed via sequencing. The DEL was delivered proportionally into PBMCs with mechanoporation. Shown is the Spearman R correlation analysis of DEL features between experimental conditions.


The correlation of diluted DEL sample with the mechanoporated sample, (Fig. 3, R2=0.93) is close to that with the technical replicate of just the DEL library (Fig. 4, R2=0.98). This is drastically greater than that with the purposefully biased target-selected DEL sample (Fig. 5, R2=0.77). The result suggests that the DEL delivered by mechanoporation is proportional to the initial DEL distribution. 

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Fig. 3: The DEL was delivered proportionally into PBMCs with mechanoporation technology. Shown is the Spearman R correlation analysis of the DEL library alone vs the DEL library after being mechanoporated into cells.
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Fig. 4: Control showing the replicate of two samples of the same DEL library
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Fig 5: DEL control vs a target biased library to demonstrate what a non proportional delivery would look like

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