Single Sperm Sequencing Assay for Prediction of Autism Risk

Background & Unmet Need

• Investigating RNA and mutations in sperm is an important tool for predicting risk of diseases such as autism spectrum disorders (ASD), which have been correlated with advanced paternal age
• Most studies have focused on the assessment of bulk sperm, where only high-frequency variants are detected
• Single-cell RNA sequencing (scRNA-seq) allows for the discovery and investigation of many cellular subtypes, but is difficult to apply to human germline tissues due to transcriptional and morphological differences from somatic cells
• Unmet Need:Methods to analyze sperm on a single-cell level to improve prediction of ASD and other diseases

Technology Overview

• The Technology: Single cell sperm sequencing assay for offspring disease risk assessments and IVF sperm sampling procedures
• Using the 10x Genomics Chromium platform, the inventors performed single-cell RNA sequencing on six donor sperm samples (scSperm-RNA-seq)
• PoC Data: Differences between the ASD and control samples revealed distinct expression landscapes and pathways that have potential to be used as biomarkers for sperm health or function
• ASD samples exhibited enrichment of genes for mTOR signaling, which has been shown to be a potential target for autism, and eIF2 signaling, which is involved in the inhibition of CREB, a transcription factor being investigated in connection with multiple neurodegenerative disorders
• This method could also be used to replace manual sperm analysis procedures performed as part of an infertility evaluation

Technology Applications

• Can be used to assess risk of autism and other diseases in future offspring
• Sperm sample assessment in fertility clinics
• Sperm analysis for animal husbandry

Technology Advantages

• Automated and accurate analysis
• Cost-effective
• Enables genetic analysis of single sperm cells