Membrane-targeted DNA frameworks with biodegradability recover cellular function and morphology from frozen cells

Area of Science:

• Biotechnology and Nanotechnology
• Cell Biology and Cryopreservation

Background:

• Long-term preservation of biological materials relies on cell freezing.
• Conventional cryoprotective agents, such as dimethyl sulfoxide (DMSO), exhibit cytotoxicity and limited efficacy.
• There is a need for advanced cryoprotective agents to improve cell recovery and viability.

Purpose of the Study:

• To introduce DNA frameworks (DFs) as a novel class of nanoengineered programmable cryoprotectants.
• To evaluate the efficacy of DFs in overcoming the limitations of conventional cryoprotective agents.
• To investigate the mechanism of cryoprotection offered by DFs.

Main Methods:

• Design and synthesis of programmable DNA frameworks (DFs) with specific structural features.
• Functionalization of DFs with cholesterol for enhanced membrane interaction.
• Assessment of cellular recovery, functionality, and morphology after cryopreservation using DFs compared to conventional agents.

Main Results:

• Cholesterol-functionalized DFs demonstrated superior performance over conventional cryoprotectants.
• DFs effectively inhibited intracellular and extracellular ice formation.
• DFs exhibited targeted binding to the cell membrane, minimizing intracellular uptake and reducing toxicity.

Conclusions:

• DNA frameworks represent a transformative advance in cell cryopreservation technology.
• DFs offer a combination of membrane-targeting specificity, cryoprotective efficacy, and biocompatibility.
• The programmable nature and biodegradability of DFs mitigate toxicity risks associated with cryopreservation.