Around the world, scientists have developed different kinds of drug for various maladies. The drug formulation has many components to it, each being developed individually before the pieces are put together for testing on a patient. One of these pieces is the drug delivery carrier. There are different materials scientists have used for this such as liposomes and polymers. DNA is one such material.
For any drug delivery carrier to be useful, it has to remain intact in the body until it can deliver the drug to the target site (for example, where the tumor is). So, they need to be “biostable”. DNA-based carriers have many advantages such as biocompatibility (i.e. not toxic) and easy functionality (i.e. other type of chemicals such as fluorescent dyes can be attached to track them within cells). However, being a natural material, DNA is vulnerable to attack by nucleases in the body (enzymes that degrade nucleic acids). To make DNA-based drug carriers more biostable, one has to make it more nuclease resistant.
In the science fiction movie, The Fifth Element, the heroine Leeloo is considered a perfect human-like being because of her 8-stranded helical DNA that is “tightly packed with infinite genetic knowledge” (see video). In reality, there are instances both in biology and biotechnology where DNA structures can have more than two strands. In our recent research, we studied whether DNA structures with multiple strands would be more biostable than regular double stranded DNA.
We analyzed a known DNA motif called paranemic crossover DNA (PX DNA). This structure has two double helical domains, containing 4 DNA strands connected together by 6 crossover points (see illustration). Compared to regular double helical structures and even other 4-stranded structures, PX DNA showed exceptional nuclease resistance when tested against different types of nucleases. That is, the PX DNA structure was intact in the presence of such nucleases for more than 1 hour, while the other structure degraded completely in a few minutes. We found that this enhanced nuclease resistance comes from the increased number of crossovers in the PX DNA structure. To establish this, we designed variations of the structure with lesser number of crossovers to determine whether the crossover number affects biostability. We tested the structures in human blood and urine, and PX DNA was the most stable (6 crossovers) followed by other structures with a lesser number of crossovers. Duplex DNA (with no crossovers) was the least stable
The take away: One can potentially introduce crossover points while designing DNA nanostructures so as to make them more biostable. This will allow the construction of robust drug delivery vehicles that can withstand physiological conditions until the drug is released at target locations in the body.
Read our scientific paper on this topic here (behind a paywall) and news coverage here.
You can read more about DNA nanotechnology here.