Science Saturday January 21, 2023June 17, 2023

#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.

KIF1A-Related Research

Diagnostic potential of the amniotic fluid cells transcriptome in deciphering mendelian disease: a proof-of-concept

Identifying a disease’s cause is a necessary step for treating that disease, which is why early genetic screening is so important for children with genetic disorders. But there are multiple barriers that can limit the use of genetic testing. But some mutations, called Variants of Uncertain Significance (VUS) are not well understood and may or may not cause disease.

One way to learn more about a Variant of Uncertain Significance is to look at the RNA produced by the mutation. RNA is transcribed from DNA and instructs the cells to make proteins (learn more in the video below); if a VUS is harmful, it’s possible it will disrupt RNA structure or expression, which could help identify disease-causing genes more easily.

While the same DNA is present across every cell in your body, RNA is only made when a cell needs it, so sampling the right cells is important for RNA sequencing. For example blood cells may not express RNA for many genes that are relevant to lung disease, while prenatal or postnatal skin samples are invasive and inconvenient.

In this week’s #ScienceSaturday, researchers analyzed RNA samples from a different source: Amniotic cells obtained during amniocentesis, a sampling of amniotic fluid after ultrasound abnormalities are detected. The authors performed RNA sequencing on amniotic cells from children with known genetic disorders to validate their technique. They found that many RNA transcripts were enriched in amniotic cells, allowing them to identify and further assess Variants of Unknown Significance in their patients. This represents a potential way to screen children for genetic disorders earlier and more easily than before.

Rare Roundup

NIH Project Aims to Make Gene Therapy ‘Playbook’ Public

There are an estimated 7,000-10,000 rare diseases in the world, and producing treatments for them all is a staggering task. Gene therapies offer one of the most direct benefits for genetic disorders by reversing DNA mutations, but they face a difficult clinical pipeline; each component of a gene therapy must be carefully tested, even components that have been tested in other disease contexts. This process slows down the approval process for therapies with different genetic targets but other identical components, which provides a particular challenge for rare disease communities.

To address this, the National Center for Advancing Translational Science (NCATS) at the National Institutes of Health launched PaVe-GT (Platform Vector Gene Therapy), which aims to develop genetic therapies for four rare diseases (specifically propionic acidemia, methylmalonic acidemia, Dok7 deficiency, and collagen Q deficiency) using a similar delivery method while creating standardized guidance and resources to develop similar treatments for other diseases. These will be valuable tools that may save time and money for rare disease communities, and also reflects the NIH’s commitment to streamlining therapeutic pipelines for genetic disorders.