GeneLancet Biosciences is developing STAR editors as one-time-cures for neurodegenerative disorders, KRAS-driven cancers and chronic viral infections.
STAR (Seek-Tag-Amend-Release) is a precise multiple-turnover genome editor for editing target genes with enhanced release of the acting ribonucleoprotein (RNP) complex. 1. Seek: a nCas9(H840A)/segNA complex binds target DNA that contains a sequence match to the first 17-20 nucleotides of the segNA and immediately before a protospacer adjacent motif (PAM) to form an R-loop. 2. Tag: cleavage and further 3’-end processing by RuvC leave a PAM distal strand of various lengths which is asymmetrically released from the nCas9:segNA:DNA complex. The released DNA strand acts as a primer and hybridizes with the 3’- homology arm of the conjugated ssDNA strand, which acts as a template for DNA repair. 3. Amend: the tagged DNA nick is repaired by ssDNA-templated synthesis and the 5’- flaps are removed and the gaps are ligated by cellular enzymes (mismatch repairing). The editing efficiency can be enhanced by a second nick at non-editing strand, the mismatches in non-editing strand can be efficiently corrected via edited-strand templated DNA synthesis, while indels can be minimal because of the high processivity of DNA polymerase. 4. Release: Cas9:segNA complex is released from the repaired DNA and ready for next cycle.
EpiSTAR is a precise epigenetic editor of single CpG resolution when segNA of methylated ssDNA is used in combination with a deactivated Cas protein.
DuoSTAR (with a segNA pair) enables diverse editing including efficient precise single base editing, deletion of nucleotides and long repeats and insertions of longer DNAs (see the figure).
DuoSTAR is a dual segNA-guided CRISPR-polymerase editor.
GeneLancet’s present pipeline in 2025-2026 (using DuoSTAR). Expansion is expected.
DuoSTAR (Cancer) is a broad-spectrum therapeutic agent designed to effectively treat a wide range of KRAS-driven cancers.