Theranostic Cells: Emerging Clinical Applications of Synthetic Biology

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2021 Jul 8

PMID 34234299

Citations 40

Authors

Monica P McNerney

Kailyn E Doiron

Tai L Ng

Timothy Z Chang

Pamela A Silver

Affiliations

Soon will be listed here.

Abstract

Synthetic biology seeks to redesign biological systems to perform novel functions in a predictable manner. Recent advances in bacterial and mammalian cell engineering include the development of cells that function in biological samples or within the body as minimally invasive diagnostics or theranostics for the real-time regulation of complex diseased states. Ex vivo and in vivo cell-based biosensors and therapeutics have been developed to target a wide range of diseases including cancer, microbiome dysbiosis and autoimmune and metabolic diseases. While probiotic therapies have advanced to clinical trials, chimeric antigen receptor (CAR) T cell therapies have received regulatory approval, exemplifying the clinical potential of cellular therapies. This Review discusses preclinical and clinical applications of bacterial and mammalian sensing and drug delivery platforms as well as the underlying biological designs that could enable new classes of cell diagnostics and therapeutics. Additionally, we describe challenges that must be overcome for more rapid and safer clinical use of engineered systems.

Citing Articles

biGMamAct: efficient CRISPR/Cas9-mediated docking of large functional DNA cargoes at the locus.

Pelosse M, Marcia M Synth Biol (Oxf). 2025; 10(1):ysaf003.

PMID: 40065842 PMC: 11891445. DOI: 10.1093/synbio/ysaf003.

Population-level amplification of gene regulation by programmable gene transfer.

Son H, Hamrick G, Shende A, Kim K, Yang K, Huang T Nat Chem Biol. 2025; .

PMID: 39779901 DOI: 10.1038/s41589-024-01817-9.

CCR5 and IL-12 co-expression in CAR T cells improves antitumor efficacy by reprogramming tumor microenvironment in solid tumors.

Tian Y, Zhang L, Ping Y, Zhang Z, Yao C, Shen C Cancer Immunol Immunother. 2025; 74(2):55.

PMID: 39751840 PMC: 11699016. DOI: 10.1007/s00262-024-03909-w.

Thermal-responsive activation of engineered bacteria to trigger antitumor immunity post microwave ablation therapy.

Wu Y, Liu B, Yan Y, Gong C, Wang K, Liu N Nat Commun. 2024; 15(1):10503.

PMID: 39627266 PMC: 11614905. DOI: 10.1038/s41467-024-54883-x.

Engineering Adhesion of the Probiotic Strain Nissle to the Fungal Pathogen .

Chamas A, Svensson C, Maneira C, Sporniak M, Figge M, Lackner G ACS Synth Biol. 2024; 13(12):4027-4039.

PMID: 39265099 PMC: 11669158. DOI: 10.1021/acssynbio.4c00466.

References

Benjamin R, Graham C, Yallop D, Jozwik A, Mirci-Danicar O, Lucchini G . Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020; 396(10266):1885-1894. PMC: 11773457. DOI: 10.1016/S0140-6736(20)32334-5. View

McNerney M, Piorino F, Michel C, Styczynski M . Active Analyte Import Improves the Dynamic Range and Sensitivity of a Vitamin B Biosensor. ACS Synth Biol. 2020; 9(2):402-411. PMC: 7186122. DOI: 10.1021/acssynbio.9b00429. View

Ye H, Xie M, Xue S, Hamri G, Yin J, Zulewski H . Self-adjusting synthetic gene circuit for correcting insulin resistance. Nat Biomed Eng. 2017; 1(1):0005. PMC: 5412959. DOI: 10.1038/s41551-016-0005. View

Ajina A, Maher J . Prospects for combined use of oncolytic viruses and CAR T-cells. J Immunother Cancer. 2017; 5(1):90. PMC: 5696728. DOI: 10.1186/s40425-017-0294-6. View

Citorik R, Mimee M, Lu T . Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol. 2014; 32(11):1141-5. PMC: 4237163. DOI: 10.1038/nbt.3011. View

Soucy S, Huang J, Gogarten J . Horizontal gene transfer: building the web of life. Nat Rev Genet. 2015; 16(8):472-82. DOI: 10.1038/nrg3962. View

Guedan S, Calderon H, Posey Jr A, Maus M . Engineering and Design of Chimeric Antigen Receptors. Mol Ther Methods Clin Dev. 2019; 12:145-156. PMC: 6330382. DOI: 10.1016/j.omtm.2018.12.009. View

Esensten J, Bluestone J, Lim W . Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials. Annu Rev Pathol. 2016; 12:305-330. PMC: 5557092. DOI: 10.1146/annurev-pathol-052016-100304. View

Sands B . Biomarkers of Inflammation in Inflammatory Bowel Disease. Gastroenterology. 2015; 149(5):1275-1285.e2. DOI: 10.1053/j.gastro.2015.07.003. View

10.

Xie M, Fussenegger M . Designing cell function: assembly of synthetic gene circuits for cell biology applications. Nat Rev Mol Cell Biol. 2018; 19(8):507-525. DOI: 10.1038/s41580-018-0024-z. View

11.

Dang L, Bettegowda C, Huso D, Kinzler K, Vogelstein B . Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci U S A. 2001; 98(26):15155-60. PMC: 64999. DOI: 10.1073/pnas.251543698. View

12.

Hong M, Clubb J, Chen Y . Engineering CAR-T Cells for Next-Generation Cancer Therapy. Cancer Cell. 2020; 38(4):473-488. DOI: 10.1016/j.ccell.2020.07.005. View

13.

Silverman A, Karim A, Jewett M . Cell-free gene expression: an expanded repertoire of applications. Nat Rev Genet. 2019; 21(3):151-170. DOI: 10.1038/s41576-019-0186-3. View

14.

Jannetto P, Fitzgerald R . Effective Use of Mass Spectrometry in the Clinical Laboratory. Clin Chem. 2015; 62(1):92-8. DOI: 10.1373/clinchem.2015.248146. View

15.

Hsu B, Way J, Silver P . Stable Neutralization of a Virulence Factor in Bacteria Using Temperate Phage in the Mammalian Gut. mSystems. 2020; 5(1). PMC: 6989128. DOI: 10.1128/mSystems.00013-20. View

16.

Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W . Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019; 178(4):795-806.e12. PMC: 7288240. DOI: 10.1016/j.cell.2019.07.008. View

17.

Ostrov N, Jimenez M, Billerbeck S, Brisbois J, Matragrano J, Ager A . A modular yeast biosensor for low-cost point-of-care pathogen detection. Sci Adv. 2017; 3(6):e1603221. PMC: 5489263. DOI: 10.1126/sciadv.1603221. View

18.

Rebar E, Huang Y, Hickey R, Nath A, Meoli D, Nath S . Induction of angiogenesis in a mouse model using engineered transcription factors. Nat Med. 2002; 8(12):1427-32. DOI: 10.1038/nm1202-795. View

19.

Watstein D, Styczynski M . Development of a Pigment-Based Whole-Cell Zinc Biosensor for Human Serum. ACS Synth Biol. 2017; 7(1):267-275. PMC: 5778388. DOI: 10.1021/acssynbio.7b00292. View

20.

Smetherman D . Screening, imaging, and image-guided biopsy techniques for breast cancer. Surg Clin North Am. 2013; 93(2):309-27. DOI: 10.1016/j.suc.2013.01.004. View