A landmark development in precision genomics: structural characterization of Cas9’s evolutionary predecessor, TnpB, spanning only 400 amino acids. ✓ Standard Cas9 exceeds the 4.7 kb genetic carrying c…
🧬 Ultra-short coding sequence: TnpB requires under 1,200 base pairs compared to 4,100 bp for conventional SpCas9.
: ~45 kDa (3.5x lighter than Cas9)
: Over 2,500 base pairs available
: Under 0.2% genome-wide
: Monogenic CNS and muscular dystrophies
A landmark development in precision genomics: structural characterization of Cas9’s evolutionary predecessor, TnpB, spanning only 400 amino acids. ✓ Standard Cas9 exceeds the 4.7 kb genetic carrying capacity of clinically approved AAV delivery vectors; ✓ TnpB’s ultra-compact size frees up over 2.5 kb of payload volume for guide RNAs and corrective donor templates; ✓ Delivers 98.5% on-target cleavage efficiency with negligible off-target chromosomal toxicity.
The miniature endonuclease leverages right-element transposon RNA (reRNA) for sequence-specific cleavage alongside 5’-PAM motifs without bulky accessory scaffolding.
Integration complexity remains the primary barrier.
By 2028, single-vector AAV clinical trials utilizing TnpB will begin targeting Duchenne muscular dystrophy in vivo.