Researchers Discover ‘Super Minigene’ that Helps Find Potential Therapies for Spinal Muscular Atrophy

For decades researchers have had to isolate segments of genes in order to study them. They called the isolated gene a “mini gene.”

Ravindra Singh, a biomedical science professor at the University of Iowa, spent many years researching a gene that, if mutated, results in spinal muscular atrophy (SMA). The disease is deadly with an average lifespan of two years. As recently reported in Newswise, it is a common genetic disease occurring in children and a leading genetic cause of infant mortality.

The new super minigene will help to find therapies for SMA (aka Werdnig-Hoffman disease) which affects one out of every 10,000 births. In its most severe form, the disease causes weak muscles and inhibits the development of motor control in infants. At the same time Professor Singh led a team of researchers on an eight-year project that created an abbreviated version of the Survival Motor Neuron 2(SMN2) gene. The project was admittedly time intensive as this was new ground to cover with no prior research that could be used as a pattern. The researchers had to examine 30 processes in order to stitch a model together.

They call the new version a “super minigene” as it is about 5-10x smaller than the natural SMN2 genes. However, despite the smaller size, the new version includes 28,000 base pairs which are two nitrogen-containing bases forming the structure of DNA. The four bases in DNA are Adenine, Cytosine, Guanine, and Thymine.

An article describing the team’s work was recently published in the research journal Nucleic Acids.
Scientists are now able to observe the way changes occur in the gene expression process. That means from transcription to translation and then to protein production.

Transcription to Translation

By definition, transcription is the process whereby DNA is copied to RNA. The process by which RNA is involved in the production of proteins is called translation. Dr. Singh explained the importance of their research. He said that to date, researchers have not been able to study the entire system. The super minigene enables scientists to study all mechanisms at once. In other words, rather than studying five systems individually, the teams get quicker and more accurate results all in one experiment.

The doctor was even more explicit as he described creating mutations and then being able to observe the entire process. He called their study results a big achievement.

A Specialty Within a Specialty

Molecular biologists may specialize in certain genetic expression areas. As an example, Professor Singh has specialized in splicing. This removes introns, which are non-coding sequences as messenger RNA forms. Professor Singh suggests that having simplified testing covering the entire gene will avoid a possible silo effect and be better at capturing interactions. The professor explains that the super mini gene’s density is mostly due to eliminating introns which are large pieces of DNA that are stuck in genes. The introns contain instructions and information about how certain proteins should be created. Certain noncoding segments are kept ensuring accuracy and stability.

Professor Singh said that each step in the process must be treated separately as each one must be optimized before they can be combined. If the fit is not right, they must “start from square one.” In 90% of the cases tested, the super minigene had results that were the same as the SMN2 gene. Professor Singh has been successful in finding potential therapies for SMA. This included a target leading to the first federally approved treatment for the disease.

The professor believes that this discovery will have an impact extending beyond SMA and that research teams may copy the process and apply it to other genes that are related to Parkinson’s or ALS for example.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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