Not so long ago most of the attention in biochemistry focused on DNA and messenger RNA or mRNA.

But in recent years there has been a shift toward proteins reflected in recent Nobel and Lasker awards. Deservedly so, given that proteins are the workhorses of cells.

Hence the recent, some would say revolutionary attention, given to harnessing artificial intelligence for predicting the shapes of proteins based on their structure. 

Proteins are constructed of chains of amino acids, the order of selection of which dictates the form, and hence function of proteins and to which other molecular groups such as sugars or nucleotides may be attached to further modify the function of the protein molecules.

Proteins play key roles, the best known of which include activating and silencing genes, providing the cytoskeletal framework for cells, transport systems for molecules in cells, highly selective transporter channels and receptors in the cell membrane — and hundreds of other functions. 

Five per cent of genes are protein-encoding: They provide the molecular blueprint for specific proteins.

Specific genes are transcribed in the nucleus to form matching mRNA, which in turn, is translated in organelles called ribosomes in the cytoplasm, then, into chains of amino acids to form the finished protein. 

Such a complex system is prone to mistakes, the most common of which are hereditary or acquired mutations in the protein-encoding genes.

The latter mutations lead to mutant forms of mRNA and therefore mutant forms of proteins that may fail to work at all or poorly. 

In the nervous system, there are many examples of mutant genes causing mutant forms of proteins and serious diseases, such as Huntington’s disease and the autosomal dominant forms of Alzheimer’s disease, both of which cause dementia, and neuromuscular diseases such as Duchenne muscular dystrophy and myotonic dystrophy.

All are serious and hard to treat, even in the present era of gene editing, which held the promise of fixing mutant genes responsible for the mutant proteins that cause these and hundreds of other protein-related diseases.

Unfortunately transforming theory into practice is difficult. For example, in the case of Duchenne dystrophy caused by a mutant version of the largest gene in the body, it’s hard to package enough CRISPR gene-editing tools into enough viral vectors, and to get enough of the latter into enough muscle tissue, to make an obvious difference clinically.

To that sobering list of linked hurdles must be added the fact that the process can’t be repeated — the initial dose prompts the development of antibodies to the viral vector that carries the gene fix.

Gene editing using CRISPR technology, which seemed so promising a few years ago, turned out in this example, to be impossible.

Fortunately, there are other ways to edit genes. Why not silence abnormal protein-encoding genes by attaching methyl groups to the genes in much the same way that nature attaches methyl groups to genes to silence them? 

That’s precisely what a team at the Massachusetts Institute of Technology, or MIT, recently set out to do.

They used zinc-finger proteins small enough to fit into benign viral vectors to activate enzymes capable of adding methyl groups to DNA, thereby silencing targeted genes in mice.

Sonia Vallabh, one of the scientists working on epigenetic gene editing, inherited the genetic mutation, which causes fatal insomnia.

Her looming fate adds urgency to the MIT team’s effort to find a way to disable her mutant genes before the disease becomes apparent in Vallabh. 

The group is also interested in using a similar epigenetic approach to silence genes in other diseases characterized by the buildup of abnormal proteins.

These include Alzheimer’s disease, Parkinson’s disease and other diseases associated with buildups of misfolded or unfolded proteins.

The latter proteins, called prions, spread to other parts of the brain by changing normal versions of proteins into similarly malformed proteins in a manner that simulates infection.  

If gene editing using similar epigenetic methods proves to be practical and effective, it may offer the first real glimmer of hope for treating horrible prion diseases such as Creutzfeldt-Jacob disease, Kuru, fatal insomnia, and mad cow disease in humans. 

This effort at MIT and other centres seeking novel means for editing genes is yet another illustration of how science works.

In 2020, Jennifer Doudna and Emmanuelle Charpentier won the Nobel Prize for pioneering work on gene editing, which adapted an ancient technique bacteria had evolved for killing off viral invaders. 

A flurry of studies followed in the wake of their pioneering work to use CRISPR Cas9 or modifications to that technique to treat hereditary diseases such as thalassemia and sickle cell anemia with some success, but in other applications was less successful because of formidable biological and technical barriers. 

Then, as in this case, other methods were developed to edit genes.

That takes time and illustrates how science works — long periods of relatively hard slogging, followed sometimes by novel breakthroughs and yet new challenges, requiring new solutions and perhaps other breakthroughs.

All depend on hard work, only a tiny fraction of which hit the headlines and lead to Nobel Prizes or their equivalent. 

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.