PEI transfection (HEK293T)

Mammalian cell culture · transfection

Cheap, efficient transfection for HEK293T (also good for HEK293, 293F). Use linear PEI MAX (Polysciences 24765, MW 40,000). About 1/100 the cost of Lipofectamine for similar yield in HEK293T.

PEI stock (1 mg/mL)

  1. Weigh 100 mg PEI MAX. Add to 90 mL endotoxin-free H₂O at room temp.
  2. Stir overnight to dissolve. Adjust to pH 7.0 with HCl (it'll start basic).
  3. Bring to 100 mL with H₂O. Filter through 0.22 µm.
  4. Aliquot 1 mL at −20 °C (long-term) or 4 °C for ~6 months (working aliquot).

Transfection (one 10 cm dish, ~5 µg DNA)

Plate formatDNAPEI (1 mg/mL)OptiMEM (or DMEM)
96-well0.1 µg0.3 µL10 µL
24-well0.5 µg1.5 µL50 µL
6-well2 µg6 µL200 µL
10 cm dish10 µg30 µL1 mL
15 cm dish25 µg75 µL2.5 mL

Ratio: 3 µL PEI per 1 µg DNA (3:1 PEI:DNA mass ratio). Tweak between 2:1 and 4:1 to optimise.

Procedure (10 cm dish, day 0 = transfection day)

  1. Day −1: Plate 4 × 10⁶ HEK293T in 10 mL DMEM-10. Should be ~70% confluent at transfection.
  2. Day 0: In a sterile 1.5 mL tube:
    • Mix 10 µg DNA + 1 mL OptiMEM (or DMEM, no FBS/antibiotic). Vortex briefly.
    • Add 30 µL PEI (3:1 mass ratio). Vortex 5 s.
  3. Incubate at room temperature 15–20 min (don't exceed 30 min — complexes aggregate).
  4. Add the entire complex dropwise to the dish. Rock gently to distribute.
  5. Return to 37 °C, 5% CO₂.
  6. Optional: change media after 4–6 h to reduce PEI toxicity (boost viability).
  7. Harvest 24–72 h post-transfection depending on your readout.

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