Direct Astrocyte-to-Neuron reprogramming using Self-amplifying RNA and RNA-based circuits

With an aging population, age-related neurological disorders like Alzheimer’s and Parkinson’s diseases, as well as stroke, are increasing. These conditions involve critical neuron loss, yet the brain’s ability to replace neurons is highly limited. Current regenerative therapies, such as neural stem cell stimulation or neuron transplants, show promise but face challenges in manufacturing and patient immunosuppression, emphasizing the need for innovative approaches.

One promising strategy involves reprogramming astrocytes—helper brain cells that proliferate during disease—into induced neurons (iNeurons). Astrocytes can be transformed into neurons by overexpressing transcription factor (TFs) that control cell DNA. However, while effective in preclinical models, AAVs are limited by their genetic payload capacity and risk of cell stress from prolonged TF expression.

Our research employs self-amplifying RNA (saRNA), a next-generation mRNA platform capable of carrying larger genetic payloads. saRNA replicates itself, enabling prolonged protein expression at minimal doses. By engineering saRNA to encode iNeuron-promoting TFs, we aim to efficiently reprogram astrocytes into functional neurons, while reducing cell stress.

Neurodegenerative diseases cause devastating physical and cognitive decline. Our saRNA platform offers a novel solution to replenish lost neurons, restore neural connections, and slow or reverse disease progression, potentially transforming treatment outcomes and improving patients’ quality of life.

Faculty Supervisor:

Anna Blakney

Student:

Partner:

University of Heidelberg

Discipline:

Life Sciences

Sector:

Biotechnology; Health and Related Sciences & Technology; Pharmaceuticals

University:

The University of British Columbia

Program: