Cut and Paste for Cancer Treatment: A DNA Nanodevice that Cuts Out an RNA Marker Sequence to Activate a Therapeutic Function Flashcards
What is the DOCTR?
The DOCTR is a multifunctional prototype DNA nanodevice that cuts out a signature sequence from the cancer marker RNA and uses it as an activator for a therapeutic function, specifically the cleavage of another RNA sequence.
What is the objective of the research regarding the development of the DNA nanorobot?
The objective is to design a DNA nanorobot for gene therapy that cleaves a housekeeping gene only in the presence of a cancer-causing point mutation, thereby suppressing cancer cells exclusively with minimal side effects to normal cells. The study aims to improve oligonucleotide gene therapy (OGT) by introducing sophisticated oligonucleotide-based nanodevices that can be more effective in anticancer treatment than traditional OGT agents.
What limitations of current technology does this nanodevice aim to address?
The limitations include the low selectivity of hybridization-based approaches under physiological conditions, the lack of clinically significant anti-cancer treatment from conventional oligonucleotide gene therapy (OGT) agents, and the potential risk of damaging healthy cells with traditional OGT agents. Additionally, the inability of traditional OGT agents to suppress cancer marker RNAs without affecting normal cells is another limitation that this nanodevice aims to address.
How does the DOCTR achieve its recognition/processing and actuating functions?
The DOCTR achieves its recognition/processing and actuating functions through a combination of DNA strands and deoxyribozymes (Dz). The recognition/processing unit of DOCTR, consisting of Dz1 and Dz2, cooperatively binds and unwinds RNA marker secondary structures, allowing for the selective recognition and processing of mutated RNA sequences. This enables the DOCTR to cut out a signature sequence from the mutated RNA, which is then used as an activator for the actuating function. The actuating function, carried out by split Dz-a and Dz-b fragments, is activated by the presence of the cut-out fragment, leading to the cleavage of another RNA sequence.
What functions does the DOCTR have in cancer treatment?
The DOCTR is equipped with recognition/processing and actuating functions, enabling it to selectively recognize and process mutated RNA sequences and activate the cleavage of another RNA, demonstrating high selectivity and potential for future anti-cancer drugs based on artificially designed nucleic acid nanostructures.
