Zorro LNA Has Potential For Blocking Genes

Scientists at the Karolinska Institute in Stockholm, Sweden, have developed a new way to block harmful genes, adding to an expanding array of gene silencing strategies that have potential for treating diseases in which something toxic, rather than something missing, is the underlying problem. (See “Defensive Action,” January-February). Most dominantly inherited conditions, in which a genetic flaw from only one parent is needed to cause symptoms, are in this category.

Rongbin Ge and colleagues, who published their results in the June issue of the FASEB (Federation of American Societies for Experimental Biology) Journal, have created a Z-shaped construct that sticks to DNA and thereby specifically silences genes in cells grown in laboratory containers. Other silencing strategies are aimed at blocking RNA, the genetic “message” derived from DNA instructions (genes). The cell uses the RNA message to create protein molecules.
 
The Swedish scientists have dubbed their compound “Zorro locked nucleic acid (LNA)” and say it sticks to each of the two strands that make up a typical stretch of DNA, as the DNA begins to “unzip” just before RNA synthesis.

RNA silencing will probably be an effective treatment for some conditions, in which only the protein product of the gene is toxic. But for disorders in which the RNA itself appears to be toxic, blocking DNA instructions is likely to be a better option. Types 1 and 2 myotonic dystrophy (MMD) are in this category.

“It’s still very early days when it comes to this technology,” said study co-author C.I. Edvard Smith, “but we are working hard to find out more about its potential. At least in the test tube and following microinjection into cells, we believe that the Zorro LNA construct has strand-invading properties. However, we still have a long way to go before we know about the clinical efficacy of this potential drug.”