Canadian Regulatory Framework and Regulatory Requirements for Cell and Gene Therapy Products.
CTO (Cells, Tissues and Organs)
Food and Drug Regulations
Food and Drugs Act
Health Canada
Homologous use
More than minimally manipulated
Regulation of cell therapy
Regulation of gene therapy
Regulations
Safety of Human Cells, Tissues and Organs for Transplantation Regulations
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
2
8
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTP) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTP, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonization at an international level are essential for progress in the development and commercialization of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking. This chapter is dedicated to provide an overview of Health Canada regulatory oversight of CGTP.
Identifiants
pubmed: 37526844
doi: 10.1007/978-3-031-34567-8_6
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
91-116Informations de copyright
© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
Government of Canada Justice Laws Website (1985) Food and Drugs Act. https://laws-lois.justice.gc.ca/eng/acts/F-27/ . Accessed 14 Jul 2022
Government of Canada Justice Laws Website Food and Drug Regulations (C.R.C., c. 870). https://laws-lois.justice.gc.ca/eng/regulations/c.r.c.,_c._870/index.html . Accessed 14 Jul 2022
Ridgway A.A.G. (2015) The regulation of cell therapy products in Canada. Biologicals 43(5):406–409
doi: 10.1016/j.biologicals.2015.05.013
pubmed: 26141550
Government of Canada Justice Laws Website (2007) Safety of Human Cells, Tissues and Organs for Transplantation Regulations. https://laws-lois.justice.gc.ca/eng/regulations/SOR-2007-118/index.html . Accessed 14 Jul 2022
Health Canada Website (2005) Drug/Medical Device Combination Products. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/policies/drug-medical-device-combination-products.html . Accessed 14 Jul 2022
Health Canada Website (2020) Assisted Human Reproduction: Prohibitions related to scientific research and clinical applications. https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/legislation-guidelines/assisted-human-reproduction/prohibitions-scientific-research-clinical-applications.html . Accessed 14 Jul 2022
Government of Canada Website (2021) Canadian Environmental Protection Act: assessment of new substances fact sheet. https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/legislation-guidelines/assisted-human-reproduction/prohibitions-scientific-research-clinical-applications.html . Accessed 11 Dec 2022
Government of Canada Website (2022) Biosafety and biosecurity. https://www.canada.ca/en/services/health/biosafety-biosecurity.html . Accessed 10 Jan 2023
Health Canada Website (2022) Regulating advanced therapeutic products. https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/regulating-advanced-therapeutic-products.html . Accessed 10 Jan 2023
ICH Official Website. https://www.ich.org/ . Accessed 7 Jan 2023
Health Canada Website (2005) Guidance for Sponsors: Lot Release Program for Schedule D (Biologic) Drugs. https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/release/guidance-sponsors-program-schedule-biologic-drugs.html . Accessed 14 Jul 2022
CAN/CSA-Z900.1:22, Cells, tissues, and organs for transplantation: general requirements (2022) Canadian Standards Association, Ottawa. https://www.csagroup.org/store/product/2701736/ . Accessed 8 Feb 2023
CAN/CSA-Z900.2.2:22, Tissues for transplantation (2022) Canadian Standards Association, Ottawa. https://www.csagroup.org/store/product/2701794/?format=PDF . Accessed 8 Feb 2023
CAN/CSA-Z900.2.3-22, Perfusable organs for transplantation (2022) Canadian Standards Association, Ottawa. https://www.csagroup.org/store/product/2701765/?format=PDF . Accessed 8 Feb 2023
CAN/CSA-Z900.2.4:22, Ocular tissues for transplantation (2022) Canadian Standards Association, Ottawa. https://www.csagroup.org/store/product/2701766/?format=PDF . Accessed 8 Feb 2023
CAN/CSA-Z900.2.5-22, Lymphohematopoietic cells for transplantation (2022) Canadian Standards Association, Ottawa. https://www.csagroup.org/store/product/2701793/?format=PDF . Accessed 8 Feb 2023
Health Canada (2020) Policy Position Paper – Autologous Cell Therapy Products. https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/cell-therapy-policy.html Accessed 22 Jul 2022
Health Canada (2008) Guidance for Industry – Priority Review of Drug Submissions. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/priority-review/drug-submissions.html . Accessed 11 Dec 2022
Health Canada (2016) Guidance Document: Notice of Compliance with Conditions (NOC/c). https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/notice-compliance-conditions.html . Accessed 11 Dec 2022
Health Canada Website (2022) Regulatory roadmap for biologic (Schedule D) drugs in Canada. https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/regulatory-roadmap-for-biologic-drugs.html . Accessed 21 Jul 2022
Health Canada (2015) Guidance Document: Preparation of Clinical Trial Applications for use of Cell Therapy. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/clinical-trials/guidance-document-preparation-clinical-trial-applications-use-cell-therapy-products-humans.html . Accessed 21 Jul 2022
International Conference on Harmonization Website (2009) ICH Considerations: General Principles to Address Virus and Vector Shedding. https://admin.ich.org/sites/default/files/2019-04/ICH_Considerations_Viral-Vector_Shedding_.pdf . Accessed 14 Jul 2022
International Conference on Harmonization Website (2009) ICH Considerations: Oncolytic Viruses. https://admin.ich.org/sites/default/files/2019-04/ICH_Considerations_Oncolytic_Viruses_rev_Sep_17_09.pdf . Accessed 14 Jul 2022
International Conference on Harmonization Website (2006) ICH Considerations: General Principles to Address the Risk of Inadvertent Germline Integration of Gene Therapy Vectors. https://admin.ich.org/sites/default/files/2019-04/ICH_Considerations_General_Principles_Risk_of_IGI_GT_Vectors.pdf . Accessed 14 Jul 2022
United States Pharmacopeia and National Formulary: Ancillary materials for cell, gene, and tissue-engineered products in ancillary reagents <1043>. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1043.html . Accessed 14 Jul 2022
United States Pharmacopeia and National Formulary: Cellular and tissue-based products <1046>. https://www.drugfuture.com/pharmacopoeia/usp35/data/v35300/usp35nf30s0_c1046.html . Accessed 14 Jul 2022
United States Pharmacopeia and National Formulary: Gene therapy products <1047>. https://www.drugfuture.com/pharmacopoeia/usp35/data/v35300/usp35nf30s0_c1047.html . Accessed 14 Jul 2022
Canadian Institutes of Health Research Website (2019) Stem Cell Research. https://cihr-irsc.gc.ca/e/15255.html . Accessed 11 Dec 2022
Health Canada (2009) Guidance Document – Quality (Chemistry and Manufacturing) Guidance: Clinical Trial Applications (CTAs) for Pharmaceuticals. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/clinical-trials/quality-chemistry-manufacturing-guidance-clinical-trial-applications-pharmaceuticals.html . Accessed 8 Jan 2023
ICH Harmonised Tripartite Guideline (1995) Quality Of Biotechnological Products: Stability Testing of Biotechnological/Biological Products Q5C. https://database.ich.org/sites/default/files/Q5C%20Guideline.pdf . Accessed 8 Jan 2023
The Human Genome Project (2022) Genome assembly GRCh38.p14. https://www.ncbi.nlm.nih.gov/data-hub/genome/GCF_000001405.40/ . Accessed 8 Jan 2023
Lanza D.G., Gaspero A., Lorenzo I. et al. (2018) Comparative analysis of single-stranded DNA donors to generate conditional null mouse alleles. BMC Biol. 16: 69. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011517/ . Accessed 8 Jan 2023
Kamiya K., Kaneda M., Sugawara T. et al. (2004) A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline. J Neurosci 24:2690–2698
doi: 10.1523/JNEUROSCI.3089-03.2004
pubmed: 15028761
pmcid: 6729532
Luo H., Zheng R., Zhao Y. et al. (2017) A dominant negative FGFR1 mutation identified in a Kallmann syndrome patient. Gene 621:1–4
doi: 10.1016/j.gene.2017.04.017
pubmed: 28411082
Schwinn M.K., Machleidt T., Zimmerman K. et al. (2018) CRISPR-Mediated Tagging of Endogenous Proteins with a Luminescent Peptide. ACS Chem. Biol. 13: 467–474
doi: 10.1021/acschembio.7b00549
pubmed: 28892606
Schwinn M.K., Steffen L.S., Zimmerman K. et al. (2020) A Simple and Scalable Strategy for Analysis of Endogenous Protein Dynamics. Sci. Rep. 10: 8953. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265437/ . Accessed 8 Jan 2023
ICH Harmonised Tripartite Guideline (1997) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals S6 (R1). https://database.ich.org/sites/default/files/S6_R1_Guideline_0.pdf . Accessed 8 Jan 2023
FDA Guidance for Industry (2013) Preclinical Assessment of Investigational Cellular and Gene Therapy Products. https://www.fda.gov/media/87564/download . Accessed 3 Dec 2022
EMA Guidelines relevant for advanced therapy medicinal products Guidelines relevant for advanced therapy medicinal products. https://www.ema.europa.eu/en/human-regulatory/research-development/advanced-therapies/guidelines-relevant-advanced-therapy-medicinal-products . Accessed 3 Dec 2022
Si X.H., Xiao L., Brown C.E. et al. (2022) Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models. Int J Mol Sci. 23(6): 3154. https://doi.org/10.3390/ijms23063154 . Accessed 8 Jan 2023
Duncan B.B., Dunbar C.E., Ishii K. (2022) Applying a clinical lens to animal models of CAR-T cell therapies. Mol. Ther Methods Clin Dev 27:17–31. https://doi.org/10.1016/j.omtm.2022.08.008
doi: 10.1016/j.omtm.2022.08.008
EMA Non-clinical testing for inadvertent germline transmission of gene transfer vectors – Scientific guideline. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-non-clinical-testing-inadvertent-germline-transmission-gene-transfer-vectors_en.pdf . Accessed 3 Dec 2022
EMA Zolgensma Assessment Report. https://www.ema.europa.eu/en/documents/assessment-report/zolgensma-epar-public-assessment-report_en.pdf . Accessed 3 Dec 2022
Sabatino D.E., Bushman F.D., Chandler R.J. et al. (2022) Evaluating the state of the science for adeno-associated virus integration: An integrated perspective. Mol. Ther. 30(8): 2646–2663
doi: 10.1016/j.ymthe.2022.06.004
pubmed: 35690906
ICH Harmonised Guideline Integrated Addendum To ICH E6 (R1) (2016) Guideline For Good Clinical Practice E6 (R2). https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf . Accessed 8 Jan 2023
Li C.H., Zhao H., Cheng L. et al. (2021) Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice. Cell Biosci. 11: 187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561357/ . Accessed 8 Jan 202347.
Bessis N., Garcia Cozar F.J., Boissier M.C. (2004) Immune responses to gene therapy vectors: influence on vector function and effector mechanisms. Gene Ther. 11: S10–S17
doi: 10.1038/sj.gt.3302364
pubmed: 15454952
Health Canada Summary Basis of Decision (SBD). https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/summary-basis-decision.html . Accessed 3 Dec 2022
Health Canada’s Clinical Trials Database. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/health-canada-clinical-trials-database.html . Accessed 3 Dec 2022
Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi. https://clinicaltrials.gov/ct2/show/NCT0404202 . Accessed 3 Dec 2022
Qualifying Notice – Abecma (2021). https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions/qualifying-notice-abecma-244266.html . Accessed 3 Dec 2022
CLIC-1901 for the Treatment of Patients with Relapsed/Refractory CD19 Positive Hematologic Malignancies (CLIC-01). https://clinicaltrials.gov/ct2/show/NCT03765177 . Accessed 4 Dec 2022
Anti-CD19, Dual Co-stimulatory (4-1BB, CD3ζ) Chimeric Antigen Receptor T-cells in Patients with Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL) (ACIT001/EXC002). https://clinicaltrials.gov/ct2/show/NCT03938987 . Accessed 4 Dec 2022
A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia. https://clinicaltrials.gov/ct2/show/NCT03330691 . Accessed 4 Dec 2022
Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients with Solid Tumors. https://clinicaltrials.gov/ct2/show/NCT02869217 . Accessed 4 Dec 2022
TAC T-cells for the Treatment of HER2-positive Solid Tumors (TACTIC-2). https://clinicaltrials.gov/ct2/show/NCT04727151 . Accessed 4 Dec 2022
Helsen C.W., Hammill J.A., Lau V.W.C. et al. (2018) The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity. Nat. Commun. 9: 3049. https://doi.org/10.1038/s41467-018-05395-y . Accessed 8 Jan 2023
Study of Allogeneic Double Negative T Cells (DNT-UHN-1) in Patients with High Risk Acute Myeloid Leukemia. https://clinicaltrials.gov/ct2/show/NCT03027102 . Accessed 4 Dec 2022
"Re-Stimulated" Tumor-Infiltrating Lymphocytes and Low-Dose Interleukin-2 Therapy in Patients with Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. https://clinicaltrials.gov/ct2/show/NCT01883297 . Accessed 4 Dec 2022
Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer (CERPASS). https://clinicaltrials.gov/ct2/show/NCT04050436 . Accessed 4 Dec 2022
Study of ONCR-177 Alone and in Combination with PD-1 Blockade in Adult Subjects With Advanced and/or Refractory Cutaneous, Subcutaneous or Metastatic Nodal Solid Tumors or with Liver Metastases of Solid Tumors. https://clinicaltrials.gov/ct2/show/NCT04348916 . Accessed 4 Dec 2022
Oncolytic MG1-MAGEA3 with Ad-MAGEA3 Vaccine in Combination with Pembrolizumab for Non-Small Cell Lung Cancer Patients. https://clinicaltrials.gov/ct2/show/NCT02879760 . Accessed 4 Dec 2022
An Open-Label, FIH Study Evaluating the Safety and Tolerability of VCTX210A Combination Product in Subjects with T1D. https://clinicaltrials.gov/ct2/show/NCT05210530 . Accessed 4 Dec 2022
The Enhanced Angiogenic Cell Therapy – Acute Myocardial Infarction Trial (ENACT-AMI). https://clinicaltrials.gov/ct2/show/NCT00936819 . Accessed 4 Dec 2022
Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention with Repeat Dosing of eNOS-enhanced EPCs (SAPPHIRE). https://clinicaltrials.gov/ct2/show/NCT03001414 . Accessed 4 Dec 2022
EDIT-301 for Autologous HSCT in Subjects with Severe Sickle Cell Disease. https://clinicaltrials.gov/ct2/show/NCT04853576 . Accessed 4 Dec 2022
Verkerk A.J., Schot R., Dumee B. et al. (2009) Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am. J. Hum. Genet. 85(1):40–52. https://doi.org/10.1016/j.ajhg.2009.06.004 . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706965/
Safety and Efficacy of TSHA-102 in Adult Females With Rett Syndrome (REVEAL Adult Study). https://clinicaltrials.gov/ct2/show/NCT05606614 . Accessed 4 Dec 2022
Amir R.E., Van den Veyver I.B., Wan M. et al. (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23(2):185–188
doi: 10.1038/13810
pubmed: 10508514
Bloemberg D., Nguyen T.., Mac Lean S. et al. (2020) A High-Throughput Method for Characterizing Novel Chimeric Antigen Receptors in Jurkat Cells. Mol. Ther. Methods Clin. Dev. 31(16):238–254
doi: 10.1016/j.omtm.2020.01.012
Ran F.A., Hsu P.D., Lin C.Y. et al. (2013) Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154:1380–1389
doi: 10.1016/j.cell.2013.08.021
pubmed: 23992846
pmcid: 3856256
Chen Y.A., Kankel M.W., Hana S. et al. (2022) In vivo genome editing using novel AAV-PHP variants rescues motor function deficits and extends survival in a SOD1-ALS mouse model. Gene Ther. https://doi.org/10.1038/s41434-022-00375-w . Accessed 8 Jan 2023
Gaj T., Ojala D.S., Ekman F.K. et al. (2017) In vivo genome editing improves motor function and extends survival in a mouse model of ALS. Sci. Adv. 3:eaar3952. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738228/ . Accessed 8 Jan 2023
Gyorgy B., Loov C., Zaborowski M.P. et al. (2018) CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer's Disease. Mol. Ther. Nucleic Acids 11:429–440
doi: 10.1016/j.omtn.2018.03.007
pubmed: 29858078
pmcid: 5992788
Ekman F.K., Ojala D.S., Adil M.M. et al. (2019) CRISPR-Cas9-Mediated Genome Editing Increases Lifespan and Improves Motor Deficits in a Huntington's Disease Mouse Model. Mol. Ther. Nucleic Acids 17:829–839
doi: 10.1016/j.omtn.2019.07.009
pubmed: 31465962
pmcid: 6717077
Monteys A.M., Ebanks S.A., Keiser M.S. et al. (2017) CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo. Mol. Ther. 25:12–23
doi: 10.1016/j.ymthe.2016.11.010
pubmed: 28129107
pmcid: 5363210
Yang S., Chang R., Yang H. et al. (2017) CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington's disease. J. Clin. Invest. 127:2719–2724
doi: 10.1172/JCI92087
pubmed: 28628038
pmcid: 5490741
Tabebordbar M., Lagerborg K.A., Stanton A. et al. (2021) Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184, 4919–4938 e4922
Rees H.A. and Liu D.R. (2018) Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19:770–788
doi: 10.1038/s41576-018-0059-1
pubmed: 30323312
pmcid: 6535181
Komor A.C., Kim Y.B., Packer M.S. et al. (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533:420–424
doi: 10.1038/nature17946
pubmed: 27096365
pmcid: 4873371
Gaudelli N.M., Komor A.C., Rees H.A. et al. (2017) Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage. Nature 551:464–471
doi: 10.1038/nature24644
pubmed: 29160308
pmcid: 5726555
Zhang X., Zhu B., Chen L. et al. (2020) Dual base editor catalyzes both cytosine and adenine base conversions in human cells. Nat. Biotechnol. 38:856–860
doi: 10.1038/s41587-020-0527-y
pubmed: 32483363
Kurt I.C., Zhou R., Iyer S. et al. (2021) CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat. Biotechnol. 39:41–46
doi: 10.1038/s41587-020-0609-x
pubmed: 32690971
Lim C.K.W., Gapinske M., Brooks A.K. et al. (2020) Treatment of a Mouse Model of ALS by In Vivo Base Editing. Mol. Ther. 28:1177–1189
doi: 10.1016/j.ymthe.2020.01.005
pubmed: 31991108
pmcid: 7132599
Levy J.M., Yeh W.H., Pendse N. et al. (2020) Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses. Nat. Biomed. Eng. 4:97–110
doi: 10.1038/s41551-019-0501-5
pubmed: 31937940
pmcid: 6980783
Grunewald J., Zhou R., Garcia S.P. et al. (2019) Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569:433–437
doi: 10.1038/s41586-019-1161-z
pubmed: 30995674
pmcid: 6657343
Zhou C., Sun Y., Yan R. et al. (2019) Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571:275–278
doi: 10.1038/s41586-019-1314-0
pubmed: 31181567
Rees H.A., Wilson C., Doman J.L. et al. (2019) Analysis and minimization of cellular RNA editing by DNA adenine base editors. Sci. Adv. 5: eaax5717. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506237/ . Accessed 8 Jan 2023
Gaudelli N.M., Lam D.K., Rees H.A. et al. (2020) Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38:892–900
doi: 10.1038/s41587-020-0491-6
pubmed: 32284586
Richter M.F., Zhao K.T., Eton E. et al. (2020) Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38:883–891
doi: 10.1038/s41587-020-0453-z
pubmed: 32433547
pmcid: 7357821
Choi E.H., Suh S., Foik A.T. et al. (2022) In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration. Nat. Commun. 13:1830. https://www.nature.com/articles/s41467-022-29490-3 . Accessed 8 Jan 2023
Chemello F., Chai A.C., Li H. et al. (2021) Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing. Sci. Adv. 7(18) https://www.science.org/doi/10.1126/sciadv.abg4910 . Accessed 8 Jan 2023
Eriksson M., Brown W.T., Gordon L.B. et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298
doi: 10.1038/nature01629
pubmed: 12714972
Koblan L.W., Erdos M.R., Wilson C. et al. (2021) In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice. Nature 589:608-614
doi: 10.1038/s41586-020-03086-7
pubmed: 33408413
pmcid: 7872200
Musunuru K., Chadwick A.C., Mizoguchi T. et al. (2021) In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593:429–434
doi: 10.1038/s41586-021-03534-y
pubmed: 34012082
Rothgangl T., Dennis M.K., Lin P.J.C. et al. (2021) In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat. Biotechnol. 39:949–957
doi: 10.1038/s41587-021-00933-4
pubmed: 34012094
pmcid: 8352781
Health Canada (2018) Notice to industry: Aligned reviews between Health Canada and health technology assessment organizations. https://www.canada.ca/en/health-canada/corporate/transparency/regulatory-transparency-and-openness/improving-review-drugs-devices/notice-aligned-reviews-health-canada-health-technology-assessment-organizations.html . Accessed 3 Nov 2022
Health Canada (2019) Notice to Industry: Health Canada and CADTH launch new initiative to provide early parallel scientific advice. https://www.canada.ca/en/health-canada/corporate/transparency/regulatory-transparency-and-openness/improving-review-drugs-devices/notice-early-panel-scientific-advice.html . Accessed 3 Nov 2022
Smith M.S.M. and Ridgway A.A.G. (1997) Tissue-engineered products: the Canadian approach. Tissue Eng. 3:85–90
doi: 10.1089/ten.1997.3.85