SCIENCE

Advanced Targeting.
Designed to Combine.

Precigen advances the promise of precision immunology through novel multifunctional gene and cell therapies designed to work in combination to achieve efficacy and safety.

Immuno-oncology
Autoimmune Disorders
Infectious Diseases

Construct

Powerful gene programs to drive efficacy

UltraVector®

UltraVector® platform incorporates advanced DNA construction technologies and computational models to design and assemble genetic components into complex gene expression programs. UltraVector-enabled matrices facilitate rapid identification of components that yield desired gene expression. Our library of characterized genetic components and associated functional characterization data enable construction of gene programs for optimized expression of multiple effector genes.

mbIL15

Membrane-bound interleukin-15, or mbIL15, is our proprietary chimeric cytokine that is engineered to be tethered to the cell surface to avoid systemic circulation. Expression of mbIL15 gene is shown to improve functional characteristics of certain immune cells, including T cells, by enhancing their potential for expansion and persistence resulting in longer lasting anti-tumor response.

Deliver

Gene programs via viral, non-viral, and microbe-based approaches to drive lower costs

Sleeping Beauty system

Sleeping Beauty is the leading non-viral transposon/transposase system to stably reprogram immune cells by inserting specific DNA sequences into the genome. Sleeping Beauty system brings the advantages of non-viral vectors that include the ease and relatively low cost of manufacturing, stability for longer-term storage, and lack of immunogenicity once inside host cells. Precigen has made significant improvements to the Sleeping Beauty system by optimizing gene elements, genetic payload capacity, and efficiency of delivery into the cells. These advancements have allowed us to develop a new class of autologous CAR-T therapy, UltraCAR-T, with expression of multiple effector genes simultaneously without the use of viral vectors.

AttSite™ recombinases

AttSite recombinases enable targeted non-viral based gene delivery for various cell therapies. AttSite recombinases allow for stable integration of therapeutic genes in a unidirectional, irreversible fashion into the host cell genome. We are optimizing AttSite recombinase technology for the next generation of cutting-edge cell therapeutic applications.

AdenoVerse™

AdenoVerse technology platform is composed of a library of highly potent, proprietary adenoviral vectors for efficient delivery of vaccine antigens and therapeutic genes and is built on a scalable manufacturing platform. AdenoVerse library includes our gorilla adenovectors, which provide a potential competitive advantage in their large payload capacity, ability for repeat administrations and generation of robust antigen-specific immune responses.

Lactococcus lactis

Lactococcus lactis, or L. lactis, is a food-grade bacterium with a long history of safe use in humans that we genetically modify to deliver biologics at local disease sites for our ActoBiotics therapeutics.

Control

Gene expression and regulation to drive safety

RheoSwitch®

The RheoSwitch Therapeutic System®, or RTS®, is the most clinically advanced gene switch system for regulation of the timing and level of gene expression in response to separately administered activator ligands, such as veledimex. The RTS® provides a mechanism to precisely control the therapeutic effect of gene and cell therapies on a patient-specific basis by modifying the timing and dose of the activator ligand.

Kill switches  

Our suite of proprietary kill switches allow selective elimination of cell therapies in vivo via administration of a kill switch activator to improve the safety profile.

Tissue-specific promoters

Our library of tissue-specific promoters restrict gene expression to the cells or tissues of therapeutic interest and has potential to improve safety profile of gene therapies.

Clinical

Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Limaye SA, et al. (2013) Cancer. 119:4268-4276.

A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Braat H, et al. (2006) Clinical Gastroenterology and Hepatology. 4:754-759.

Preclinical

Reversal of diabetes in NOD mice by clinical-grade proinsulin and IL-10-secreting Lactococcus lactis in combination with low-lose anti-CD3 depends on the Induction of Foxp3-Positive T cells. Takiishi T, et al. (2017) Diabetes. 66:448-459.

Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Robert S, et al. (2014) Diabetes. 63:2876-2887.

Reversal of autoimmune diabetes by restoration of antigen- specific tolerance using genetically modified Lactococcus lactis in mice. Takiishi T, et al. (2012) Journal of Clinical Investigation. 122:1717-25.

AG013, a mouth rinse formulation of Lactococcus lactis secreting human Trefoil Factor 1, provides a safe and efficacious therapeutic tool for treating oral mucositis. Caulwaerts S, et al. (2010) Oral Oncology. 46:564-70.

Induction of antigen-specific tolerance by oral administration of Lactococcus lactis delivered immunodominant DQ8-restricted gliadin peptide in sensitized nonobese diabetic ABo DQ8 transgenic mice. Huibregtse IL, et al. (2009) Journal of Immunology. 183:2390-6.

Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. Vandenbroucke K, et al. (2010) Mucosal Immunology. 3:49-56. PMID: 19794409.

Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Vandenbroucke K, et al. (2004) Gastroenterology. 127:502-513.

Platform

Modulation of gut-associated lymphoid tissue functions with genetically modified Lactococcus lactis. Rottiers P, De Smedt T and Steidler L. (2009) International Reviews of Immunology. 28:465-486.

Induction of ovalbumin-specific tolerance by oral administration of Lactococcus lactis secreting ovalbumin. Huibregtse IL, et al. (2007) Gastroenterology. 133:517-528.

Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Steidler L, et al. (2003) Nature Biotechnology. 21:785-789.

Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Steidler L, et al. (2000) Science. 289:1352-1355.

A gorilla adenovirus-based vaccine against Zika virus induces durable immunity and confers protection in pregnancy. Hassan, et al. (2019) Cell Reports. 28:2634-2646.

Genetic vaccine for respiratory syncytial virus provides protection without disease potentiation. Johnson, et al. (2014) Mol Ther. 22:196-205.

Adenoviruses isolated from wild gorillas are closely related to human species C viruses. McVey, et al. (2013) Virology. 444:119-123.

Utilization of site-specific recombination for generating therapeutic protein producing cell lines. Campbell, et al. (2010) Molecular Biotechnology. 45:199-202. PMID: 20300883.

Phage Bxb1 integrase mediates highly efficient site-specific recombination in mammalian cells. Russell, et al. (2006) Biotechniques. 40:460, 462, 464. PMID: 16629393.

Non-viral UltraVector®

Safety of first in human triple-gene therapy candidate for heart failure patients. Jaruga-Killeen E, et al. (2019) Circulation. 140:A16296. Abstract 16296.

First human experience with novel triple effector gene therapy for heart failure. Reed TD, et al. (2019) Mol Ther. 27(4S1):360. Abstract 772.

Retrograde delivery of novel triple effector pDNA gene therapy for heart failure. Reed TD, et al. (2019) Mol Ther. 27(4S1):361. Abstract 775.

Human cardiac iPSC evaluation of novel triple effector gene therapy for dilated cardiomyopathy. Patel DS, et al. (2019) Mol Ther. 27(4S1):362. Abstract 777.

Minimally invasive novel triple effector gene therapy for Adriamycin cardiomyopathy. Grayburn PA, et al. (2019) Mol Ther. 27(4S1):363. Abstract 780.

Retrograde Coronary Sinus Infusion

Catheter-based retrograde coronary sinus infusion is a practical delivery technique for introducing biological molecules into the cardiac system. Rodenberg, et al. (2019) Catheter Cardiovasc Interv. 94:669-676. PMID: 30866153.

Neurodegeneration

Genetic ataxia telangiectasia porcine model pheno copies the multisystemic features of the human disease. Beraldi, et al. (2017) Biochim Biophys Acta Mol Basis Dis. 1863:2862-2870. PMID: 28746835.

A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease. Beraldi, et al. (2015) Hum Mol Genet. PMID: 26374845.

Neuromuscular

Dystrophin exon 52-deleted pigs as a new animal model of Duchenne muscular dystrophy: its characterization and potential as a tool for developing exon skipping therapy. Echigoya, et al. (2016) Molecular Therapy: Musculo-Skeletal Diseases II. 24:S247.

Heart Disease

H19 induces abdominal aortic aneurysm development and progression. Li, et al. (2018) Circulation. 138:1551-1568. PMID: 29669788.

Novel large animal model of xanthoma formation. Wang, et al. (2016) J Dermatol Sci. 81:203-5. PMID: 26692468.

A translational model for diet-related atherosclerosis: effect of statins on hypercholesterolemia and atherosclerosis in a minipig. Amuzie, et al. (2016) Toxicol Pathol. 44:442-9. PMID: 26883155.

Bempedoic acid lowers low-density lipoprotein cholesterol and attenuates atherosclerosis in low-density lipoprotein receptor-deficient (LDLR+/- and LDLR-/-) Yucatan miniature pigs. Burke, et al. (2018) Arterioscler Thromb Vasc Biol. 38:1178-90. PMID: 29449335.

Targeted disruption of LDLR causes hypercholesterolemia and atherosclerosis in Yucatan miniature pigs. Davis, et al. (2014) PLoS One. 9:e93457. PMID: 24691380.

Nervous System

Longitudinal phenotype development in a minipig model of neurofibromatosis type 1. Uthoff, et al. (2020) Scientific Reports. 19;10(1):5046. PMID: 32193437.

Assessment of nociception and related quality of life measures in a porcine model of neurofibromatosis type 1. Khanna, et al. (2019) Pain. 160:2473-86. PMID: 31246731.

A porcine model of neurofibromatosis type 1 that mimics the human disease. White, et al. (2019) JCI Insight. 3:e120402. PMID: 29925695.

Cancer (TP53)

Development and translational imaging of a TP53 porcine tumorigenesis model. Sieren, et al. (2014) J Clin Invest. 124:4052-66. PMID: 25105366.

Cystic Fibrosis (CFTR)

Airway submucosal glands from cystic fibrosis swine suffer from abnormal ion transport across the serous acini, collecting duct and ciliated duct. Luan, et al. (2020) Am J Physiol Lung Cell Mol Physiol. PMID: 32130033.

Airway surface liquid has innate antiviral activity that is reduced in cystic fibrosis. Berkebile, et al. (2020) Am J Respir Cell Mol Biol. 62(1):104-111. PMID: 31242392.

Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia. Muraglia, et al. (2019) Nature 567(7748):405-408. PMID: 30867598.

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens. Luan, et al. (2017) Nat Commun. 8(1):786. PMID: 28983075.

Lentiviral-mediated phenotypic correction of cystic fibrosis pigs. Cooney, et al. (2016) JCI Insight. 8;1(14). pii: 88730. PMID: 27656681.

Acidic pH increases airway surface liquid viscosity in cystic fibrosis. Tang, et al. (2016) J Clin Invest. 126(3):879-91. PMID: 26808501.

Origins of cystic fibrosis lung disease. Stoltz, et al. (2015) N Engl J Med. 372(4):351-62. PMID: 25607428.

Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Hoegger, et al. (2014) Science. 345(6198):818-22. PMID: 25124441.

A functional anatomic defect of the cystic fibrosis airway. Birket, et al. (2014) Am J Respir Crit Care Med. 190(4):421-32. PMID: 25029666.

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs. Stoltz, et al. (2013) J Clin Invest. 123(6):2685-93. PMID: 23676501.

CFTR-deficient pigs display peripheral nervous system defects at birth. Reznikov, et al. (2013) Proc Natl Acad Sci U S A. 110(8):3083-8. PMID: 23382208.

Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Pezzulo, et al. (2012) Nature. 487(7405):109-13. PMID: 22763554.

The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs. Ostedgaard, et al. (2011) Sci Transl Med. 3(74):74ra24. PMID: 21411740.

Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia. Chen, et al. 2010. Cell. 143(6):911-23. PMID: 21145458.

Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth. Rogan, et al. (2010) Proc Natl Acad Sci U S A. 107(47):20571-5. PMID: 21059918.

Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Stoltz, et al. (2010) Sci Transl Med. 2(29):29ra31. PMID: 20427821.

Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Rogers, et al. (2008) Science. 321(5897):1837-41. PMID: 18818360.

Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. Rogers, et al. (2008) J Clin Invest. 118(4):1571-7. PMID: 18324337.

Regulated intratumoral expression of IL-12 using a RheoSwitch Therapeutic System® (RTS®) gene switch as gene therapy for the treatment of glioma. Barrett, et al. (2018) Cancer Gene Therapy. 25:106-116. PMID: 29755109.

In vitro and in vivo testing of a novel regulatory system for gene therapy for intervertebral disc degeneration. Sowa, et al. (2011) Spine. 36:E623-8. PMID: 21224765.

Controlled expression of functional miR-122 with a ligand inducible expression system. Shea, et al. (2010) BMC Biotechnology. 10:76. PMID: 20961424.

Inducible mutant huntingtin expression in HN10 cells reproduces Huntington’s disease-like neuronal dysfunction. Weiss, et al. (2009) Molecular Neurodegeneration. 4:11. PMID: 19203385.

Semi-synthetic ecdysteroids as gene-switch actuators: synthesis, structure-activity relationships, and prospective ADME properties. Lapenna, et al. (2009) ChemMedChem. 4:55. PMID: 19065574.

Characterization of the RSL1-dependent conditional expression system in LNCaP prostate cancer cells and development of a single vector format. Lessard, et al. (2007) Prostate. 67:808-19. PMID: 17373718.

UltraCAR-T®

A Phase 1/1b Safety Study of Prgn-3006 Ultracar-T™ in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome. Sallman, D. et al. Blood (2020) 136 (Supplement 1): 17. 62nd Annual Meeting and Exposition of the American Society of Hematology, Abstract 2864.

PRGN-3005 UltraCAR-T®: Multigenic CAR-T cells generated using non-viral gene delivery and rapid manufacturing process for the treatment of ovarian cancer. Chan, et al. (2020) American Association for Cancer Research Virtual Annual Meeting II. Abstract 6593.

Preclinical characterization of PRGN-3006 UltraCar-T® for the Treatment of AML and MDS: non-viral, multigenic autologous CAR-T cells administered one day after gene transfer. Chan, et al. (2019) Blood. 134:2660.

Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Hurton, et al. (2016) Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7788-E7797. Epub 2016 Nov 14. PMID: 27849617

Sleeping Beauty System

Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. Hackett, et al. (2013) Translational Research. 161:265-83. PMID: 23313630.

Genome-wide Profiling Reveals Remarkable Parallels Between Insertion Site Selection Properties of the MLV Retrovirus and the piggyBac Transposon in Primary Human CD4(+) T Cells. Gogol-Döring, et al. (2016) Mol Ther. 2016 Mar;24(3):592-606. doi: 10.1038/mt.2016.11. Epub 2016 Jan 12. PMID: 26755332

Comparison of lentiviral and sleeping beauty mediated αβ T cell receptor gene transfer. Field, et al. (2013) PLoS One. 2013 Jun 28;8(6):e68201. doi: 10.1371/journal.pone.0068201. Print 2013. PMID: 23840834

Gene transfer efficiency and genome-wide integration profiling of Sleeping Beauty, Tol2, and piggyBac transposons in human primary T cells. Huang, et. al (2010) Mol Ther. 2010 Oct;18(10):1803-13. doi: 10.1038/mt.2010.141. Epub 2010 Jul 6. PMID: 20606646