System

Description

TSRA-196

Two chemically modified RNA drug substances formulated in a lipid nanoparticle delivery vehicle. The two chemically modified RNA drug substances are:

• A messenger RNA encoding a nickase Cas enzyme (that introduces a single-strand DNA break) fused to a reverse transcriptase domain, linked via a protein linker.
• A template guide RNA directing the gene editing correction of the Alpha-1 antitrypsin gene PiZ genomic variant back to the PiM wild type sequence.

and is incapable of self-replication, in whole, or in part.

Other target-primed reverse transcriptase/prime editing systems

Two or more RNA molecules, which can be chemically modified or contain non-standard nucleotides, formulated in a lipid nanoparticle delivery vehicle, as described below:

• One or more messenger RNA molecules encoding a nickase Cas enzyme (that introduces a single-strand DNA break) fused to a reverse transcriptase domain, and potentially other protein domain fusions, linked via protein linkers.
• One or more additional messenger RNA molecules intended to enhance the effectiveness of the prime editing process.
• One or more template guide RNA molecules directing one or more gene editing changes to a specific genomic locus (eg, a gene) from its native sequence to a desired new sequence.

and is incapable of self-replication, in whole, or in part.