Custom Lipid-DNA Conjugation Service

Lipid-DNA Conjugates

Lipids and DNA are the two major components of life. Interestingly, by chemically linking these two natural compounds together, the synthesized lipid DNA conjugate exhibits some attractive properties for cell membrane research. These lipid DNA conjugates are amphiphilic macromolecules that combine the cell membrane insertion ability of lipids with the precise hybridization and programmability of DNA. These supramolecular conjugates have shown exciting application prospects, from constructing cell membrane nanopores to transmembrane cargo transportation, from analyzing cell membrane events to tissue engineering.

Figure 1 Lipid and Peptide-Oligonucleotide Conjugates for Therapeutic Purposes.¹

Types of Lipids for Lipid-DNA Conjugates

Lipids are a group of naturally occurring organic molecules that play a crucial role in biology. Lipids are mainly composed of carbon, hydrogen, and oxygen atoms, and have hydrophobicity or amphiphilicity, which means they are largely insoluble in water but soluble in non-polar solvents. This unique feature is due to their long hydrocarbon chains or rings, which dominate their structure.

Why Choose Lipid Conjugation?

The strategic choice of lipid DNA coupling has many advantages over traditional biological coupling methods, making it the preferred method for next-generation drug delivery and cell engineering.

• Enhanced Cellular Uptake and Bioavailability: The main benefit is a significant increase in cellular internalization. By utilizing the natural interaction between lipids and cell membranes, these complexes have higher absorption efficiency compared to unbound nucleic acids or partially connected nucleic acids with lower membrane compatibility.
• Anchoring to Lipid Nanostructures: this is the basic principle of modern lipid nanoparticles (LNP) technology for mRNA vaccines (such as COVID-19 vaccine). Lipid DNA conjugates can incorporate LNP during the preparation process, effectively anchoring DNA onto the surface of particles. This displays DNA function externally, while the LNP core protects and delivers another payload (such as siRNA or mRNA) internally.
• Precise Spatial Organization: Unlike electrostatic encapsulation, conjugation provides stoichiometric control and predictable orientation of surface nucleic acids, which is crucial for constructing biosensors, arranging nanostructures, or engineering synthetic intercellular communication networks.

Lipid-DNA Conjugates for Cell Membrane Modification, Analysis, And Regulation

The true power of lipid DNA conjugates goes far beyond simple delivery; They are transformative tools for membrane engineering.

Cell membrane modification and "DNAization"

By simply incubating cells with lipid DNA conjugates, researchers can effectively "draw" the outer lobules of the cell membrane with oligonucleotides. This process is sometimes referred to as "DNAlization", which produces a highly programmable artificial glycocalyx. These surface bound DNA strands can be used for:

• Cell Assembly
• Actuation and Sensing

Membrane Analysis and Tracking

• Single molecule tracking: Attaching fluorescent groups to DNA can accurately track the diffusion and organization of lipids within the membrane, thereby revealing lipid raft dynamics and membrane heterogeneity.
• Adjacent markers: Lipid anchors locate DNA chains onto the membrane and can then hybridize with complementary chains linked to enzymes. This system can be used for local enzyme reactions to label and identify proximal membrane proteins.

Membrane Regulation and Therapeutic Intervention

• Targeted delivery: A lipid DNA conjugate can be designed to display an adapter that specifically binds to receptors on target cells. This guides the entire construct (as well as any attached cargo) to specific cell types, enhancing therapeutic specificity and reducing off target effects.
• Mechanical transduction: A DNA based tension probe array can be displayed on the cell surface through lipid anchoring to measure and manipulate the skin Newton level forces exerted by cells during migration and differentiation processes.

Overview of What Creative Biolabs Can Provide

Creative Biolabs provides enzyme labeling of DNA and chemical modification of nucleic acids and oligonucleotides. These chemically modified oligonucleotides are very useful in fixing conformation by introducing crosslinking agents into DNA or nucleic acid biomolecule complexes. Site specific crosslinking allows for the determination of the proximity of nucleotides or amino acids, as crosslinking at distances greater than the length of the spacer is not possible. In most cases, such reagents typically adhere to the alkaline or sugar moiety.

• Customize liposome composition, size, and surface properties.
• Modify DNA to achieve specific sequences and functions.
• Efficiently encapsulate DNA into liposomes.
• Physicochemical characterization of lipid-DNA complexes.
• Evaluate in vitro cellular uptake and intracellular distribution of complexes.
• Enhance cellular uptake and intracellular delivery.
• Determine the controlled-release kinetics of encapsulated cargo DNA.
• Provide expert guidance and consulting on formulation design.
• Customize surface modifications to achieve specific cell targeting.
• Evaluate stability under physiological conditions.
• Construct lipid-DNA hybrids.
• Comprehensive characterization using state-of-the-art analytical methods.

What Makes Creative Biolabs Your Top Choice

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