DNA ticker tape memory

“DNA molecular ticker tape” denotes schemes that transduce fast, analog biological signals into a writable nucleic-acid substrate so that time-varying activity is later recovered by sequencing and algorithmic “nucleotide-time alignment.” Early articulations (Marblestone, Kording, Boyden, Church and colleagues) framed polymerase-based recorders whose misincorporation spectra or elongation rates are modulated by intracellular variables (e.g., Ca²⁺), together with decoders that invert noisy polymerase kinetics to reconstruct the input waveform under realistic biophysical constraints.PMC, PLOS Subsequent theory introduced dynamic-time-warping alignment and design rules for start-time synchronization and polymerase speed/infidelity, thereby formalizing limits on temporal precision and bandwidth.PLOS Experimentally, the most direct “ticker” advance uses terminal deoxynucleotidyl transferase (TdT) to encode environmental cues including divalent ions such as Ca²⁺—into growing DNA with ∼minute-scale timing, demonstrating stimulus-to-DNA transduction and ratiometric decoding in vitro.PMC, PubMed In parallel, sequential genome-editing recorders (e.g., prime-editing–based DNA "typewriter") trade millisecond resolution for capacity and robustness, writing ordered, multisymbol histories into genomic “tapes” that can capture event order (not unlike lineage tracing) and dosing in cells.Nature For in vivo neuronal contexts, current molecular approaches emphasize integrative tagging (e.g., light- and Ca²⁺-gated FLiCRE) or protein-chain “expression recording islands,” which report activity histories on minutes-to-days timescales rather than spike-resolved tickers.ScienceDirect, Nature Comprehensive reviews consider CRISPR acquisition/base-editing tapes, polymerase-based tickers, and transcriptional/protein recorders and highlight remaining challenges: coupling to fast neural variables, controlling initiation/clocking, error models under cellular conditions, and scalable readout.Nature, PMC

retro-cascoder: Recording gene expression order in DNA by CRISPR addition of retron barcodes "Here we report a molecular system for making time-ordered recordings of transcriptional events into living genomes. We do this via engineered RNA barcodes, based on prokaryotic retrons, which are reverse-transcribed into DNA and integrated into the genome using the CRISPR-Cas system. The unidirectional integration of barcodes by CRISPR integrases enables reconstruction of transcriptional event timing based on a physical record via simple, logical rules rather than relying on pre-trained classifiers or post-hoc inferential methods."

Molecular recording using DNA typewriter protocol (2024)

Analysis and control of untemplated DNA polymerase activity for guided synthesis of kilobase-scale DNA sequences (2024)

Toward DNA-based recording of biological processes (2024)

Molecular recording: Transcriptional data collection into the genome (2024)

TODO: Where is the George Church quote about using an insect brain for surveillance purposes, recording action potentials in each neuron through DNA ticker tape technology, and then using DNA sequencing to reconstruct the video surveillance data later? Was this from an hgp-write conference? It's probably in the IRC logs...

See also lineage tracing, mapseq, and gene editing for other possible mechanisms for in vivo cellular event recording. You can just camp the list of new gene editing techniques and if you're fast enough then you can get the next grant for moving forward a technique like MAPseq, ISS, in situ cellular event recording, synthetic morphogenesis/developmental biology etc, since all of those advancements are going to be downstream of new clever ways of gene editing which are themselves downstream of new clever fusion proteins.