Nucleic acid modification with tools from Oxytricha

This technology identifies the enzyme responsible for adenine methylation on DNA in Oxytricha and other ciliates.

Unmet Need: Directed DNA methylation

The modified base containing N6-methyladenine (m6dA) was recently discovered in humans. The levels of md6A are significantly reduced in gastric and liver cancer tissues and disruption of m6dA promotes tumor formation. However, the exact physiological role of m6dA and the mechanism by which this base modification occurs are unknown. Therefore, there is a need for tools that enable targeted DNA methylation for creating model systems that can elucidate mechanisms of genome stability and carcinogenesis in humans.

The Technology: Ciliate enzyme enables fast, cost-effective synthesis of m6dA-containing DNA

This technology identifies the ciliate enzyme responsible for m6dA methylation on DNA in Oxytricha and the related ciliate Tetrahymena thermophila. This enzyme’s unique specificity for the deposition of dimethylated AT (5’-AT-3’ / 3’-TA-5’) may be used to generate DNA substrates containing m6dA at locations distinct from known m6dA methyltransferases, circumventing the need for slow, expensive synthesis of methylated DNA. Additionally, the technology may contribute to the rational design of N6-adenine methylating enzymes with unique substrate specificities.

Applications:

• Tool for generating methylated DNA containing m6dA at locations distinct from known methyltransferases
• Rational design of N6-adenine methylating enzymes with unique substrate specificities
• Model system for elucidating complex events that regulate genome stability, including cancer-causing events in humans

Advantages:

• Unique specificity for the deposition of dimethylated AT
• Can generate DNA substrates containing m6dA at locations distinct from known m6dA methyltransferases
• Cost-effective
• Fast synthesis of m6dA-containing methylated DNA
• Evolutionarily distinct from all known m6dA methyltransferases

Lead Inventor:

Laura Landweber, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Fang W, Wang X, Bracht JR, Nowacki M, Landweber LF. “Piwi-interacting RNAs protect DNA against loss during Oxytricha genome rearrangement“ Cell. 2012 Dec 7; 151(6): 1243-1255.

Tech Ventures Reference:

• IR CU19015

• Licensing Contact: Jerry Kokoshka