Scientists in India have made a series of modified nucleic acids that show potential as gene-targeted drugs.

Vaijayanti Kumar and colleagues at the National Chemical Laboratory in Pune synthesised thioacetamido nucleic acids (TANA) by connecting a group of nucleoside monomers to form a sugar-thioacetamide backbone. The team used the TANA in thermal stability studies with complementary DNA and RNA sequences and found that the TANA show a marked preference for binding RNA. 

Given this RNA affinity, Kumar suggested that the TANA could be used in antisense therapy, where a drug molecule binds to target RNA and inhibits protein synthesis. For good therapeutic activity the binding molecule should have 'specific recognition properties and a stable lead structure that could be cell membrane-penetrating,' he said. In addition to selective RNA binding, the nucleic acids are easy to make and the sulfur in their backbone could give them a good bioavailability, said Kumar. 

Daniel Appella at the National Institute of Diabetes & Digestive & Kidney Diseases, US, welcomed the findings. The work 'represents an important step forward in finding the ideal combination of backbone and nucleobases to afford antisense molecules that bind strongly and selectively to complementary RNA,' he said.

The challenge now is to examine the biological activity of the molecules, explained Appella. 'The high binding affinity of the TANA to RNA will likely block protein expression of specific genes. Demonstrating this effect in vitro and in vivo will be the next important steps,' said Appella.

Alison Stoddart