US 2022/0177911 A1Published application

Synthetic circuit for cellular multistability

OwnerRonghui Zhu, Michael B. Elowitzinventors

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Abstract

Disclosed herein include circuits, compositions, nucleic acids, populations, systems, and methods enabling single circuits to generate multiple molecularly and functionally distinct states that are each stable across multiple cell division cycles. Synthetic circuits provided herein can stably exist in multiple distinct states characterized by differences in the concentrations and expression levels of its components. In the absence of changes to the external environment, each of these states can be stable. In some embodiments, transcription factors provided herein activate when dimerized, and show much weaker activity as monomers. In some embodiments, each transcription factor homodimer activates expression of its own gene. In some embodiments, transcription factors can form mixed heterodimers with one another that do not strongly activate any genes in the circuit. Different embodiments of the synthetic circuits provided herein can use different numbers of transcription factors to produce a growing number of stable states.

Claims20

Dependent claims

A nucleic acid composition, comprising:

a first promoter operably linked to a first polynucleotide encoding a first transcription factor (TF) and to a second polynucleotide encoding one or more first payloads,
wherein the first promoter comprises one or more pairs of first TF binding sites, and
wherein the first TF comprises a first DNA-binding domain capable of binding a first TF binding site;
a second promoter operably linked to a third polynucleotide encoding a second transcription factor (TF) and to a fourth polynucleotide encoding one or more second payloads,
wherein the second promoter comprises one or more pairs of second TF binding sites, and
wherein the second TF comprises a second DNA-binding domain capable of binding a second TF binding site;
and
a third promoter operably linked to a fifth polynucleotide encoding a third transcription factor (TF) and to a sixth polynucleotide encoding one or more third payloads,
wherein the third promoter comprises one or more pairs of third TF binding sites, and
wherein the third TF comprises a third DNA-binding domain capable of binding a third TF binding site.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/544,865Filed 7 Dec 2021
Priority: 8 Dec 2020
Published: 9 Jun 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07K 14/4702
Not used: regulators; Modulating activity
C12N 15/85
Vectors or expression systems specially adapted for eukaryotic hosts: for animal cells
A61K 31/7105
Compounds having three or more nucleosides or nucleotides: natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine,…
A61P 35/00
Antineoplastic agents