@article{Cloarec-Ung_Beaulieu_Suthananthan_Lehnertz_Sauvageau_Sheppard_Knapp_2024,
title = {
Near-perfect precise on-target editing of human hematopoietic stem and
progenitor cells
},
author = {
Cloarec-Ung, Fanny-Mei and Beaulieu, Jamie and Suthananthan, Arunan and
Lehnertz, Bernhard and Sauvageau, Guy and Sheppard, Hilary M. and Knapp,
David J. H. F.
},
year = 2024,
month = jun,
journal = {eLife},
volume = 12,
pages = {RP91288},
doi = {10.7554/eLife.91288},
issn = {2050-084X},
abstractnote = {
Precision gene editing in primary hematopoietic stem and progenitor cells
(HSPCs) would facilitate both curative treatments for monogenic disorders as
well as disease modelling. Precise efficiencies even with the CRISPR/Cas
system, however, remain limited. Through an optimization of guide RNA
delivery, donor design, and additives, we have now obtained mean precise
editing efficiencies >90% on primary cord blood HSCPs with minimal toxicity
and without observed off-target editing. The main protocol modifications
needed to achieve such high efficiencies were the addition of the DNA-PK
inhibitor AZD7648, and the inclusion of spacer-breaking silent mutations in
the donor in addition to mutations disrupting the PAM sequence. Critically,
editing was even across the progenitor hierarchy, did not substantially
distort the hierarchy or affect lineage outputs in colony-forming cell assays
or the frequency of high self-renewal potential long-term culture initiating
cells. As modelling of many diseases requires heterozygosity, we also
demonstrated that the overall editing and zygosity can be tuned by adding in
defined mixtures of mutant and wild-type donors. With these optimizations,
editing at near-perfect efficiency can now be accomplished directly in human
HSPCs. This will open new avenues in both therapeutic strategies and disease
modelling.
},
language = {eng}
}
@article{Nelson_Randolph_Shen_Everette_Chen_Anzalone_An_Newby_Chen_Hsu_et,
title = {Engineered pegRNAs improve prime editing efficiency},
author = {
Nelson, James W. and Randolph, Peyton B. and Shen, Simon P. and Everette,
Kelcee A. and Chen, Peter J. and Anzalone, Andrew V. and An, Meirui and
Newby, Gregory A. and Chen, Jonathan C. and Hsu, Alvin and Liu, David R.
},
year = 2022,
month = mar,
journal = {Nature Biotechnology},
publisher = {Nature Publishing Group},
volume = 40,
number = 3,
pages = {402–410},
doi = {10.1038/s41587-021-01039-7},
issn = {1546-1696},
rights = {
2021 The Author(s), under exclusive licence to Springer Nature America, Inc.
},
abstractnote = {
Prime editing enables the installation of virtually any combination of point
mutations, small insertions or small deletions in the DNA of living cells. A
prime editing guide RNA (pegRNA) directs the prime editor protein to the
targeted locus and also encodes the desired edit. Here we show that
degradation of the 3′ region of the pegRNA that contains the reverse
transcriptase template and the primer binding site can poison the activity of
prime editing systems, impeding editing efficiency. We incorporated
structured RNA motifs to the 3′ terminus of pegRNAs that enhance their
stability and prevent degradation of the 3′ extension. The resulting
engineered pegRNAs (epegRNAs) improve prime editing efficiency 3–4-fold in
HeLa, U2OS and K562 cells and in primary human fibroblasts without increasing
off-target editing activity. We optimized the choice of 3′ structural motif
and developed pegLIT, a computational tool to identify non-interfering
nucleotide linkers between pegRNAs and 3′ motifs. Finally, we showed that
epegRNAs enhance the efficiency of the installation or correction of
disease-relevant mutations.
},
language = {en}
}
@article{Doench_Fusi_Sullender_Hegde_Vaimberg_Donovan_Smith_Tothova_Wilen_Orchard_et,
title = {
Optimized sgRNA design to maximize activity and minimize off-target effects
of CRISPR-Cas9
},
author = {
Doench, John G. and Fusi, Nicolo and Sullender, Meagan and Hegde, Mudra and
Vaimberg, Emma W. and Donovan, Katherine F. and Smith, Ian and Tothova,
Zuzana and Wilen, Craig and Orchard, Robert and Virgin, Herbert W. and
Listgarten, Jennifer and Root, David E.
},
year = 2016,
month = feb,
journal = {Nature Biotechnology},
publisher = {Nature Publishing Group},
volume = 34,
number = 2,
pages = {184–191},
doi = {10.1038/nbt.3437},
issn = {1546-1696},
rights = {2015 Springer Nature America, Inc.},
abstractnote = {
Genome-wide sgRNA libraries based on rules for on-target activity improve
results of Cas9-based screens and facilitate a further refinement of on- and
off-target prediction algorithms.
},
language = {en}
}
@article{White_Sadeeshkumar_Sun_Sudarsan_Breaker_2022,
title = {
Na+ riboswitches regulate genes for diverse physiological processes in
bacteria
},
author = {
White, Neil and Sadeeshkumar, Harini and Sun, Anna and Sudarsan, Narasimhan
and Breaker, Ronald R.
},
year = 2022,
month = aug,
journal = {Nature Chemical Biology},
publisher = {Nature Publishing Group},
volume = 18,
number = 88,
pages = {878–885},
doi = {10.1038/s41589-022-01086-4},
issn = {1552-4469},
rights = {2022 The Author(s)},
abstractnote = {
Only one protein factor is known that senses Na+ and controls gene
expression. The Breaker Laboratory describes a bacterial riboswitch class
selective for Na+ that regulates genes important for Na+ homeostasis, pH
maintenance, osmotic stress response and ATP synthesis.
},
language = {en}
}
@article{Iwawaki_Akai_2006,
title = {
Analysis of the XBP1 splicing mechanism using endoplasmic reticulum
stress-indicators
},
author = {Iwawaki, Takao and Akai, Ryoko},
year = 2006,
month = nov,
journal = {Biochemical and Biophysical Research Communications},
volume = 350,
number = 3,
pages = {709–715},
doi = {10.1016/j.bbrc.2006.09.100},
issn = {0006-291X},
abstractnote = {
Under endoplasmic reticulum (ER) stress conditions, XBP1 mRNA is processed by
unconventional splicing and translated into a functional transcription
factor. ER stress-specific XBP1 splicing is also known to be activated by
IRE1. However, many aspects of the molecular mechanism of XBP1 splicing
remain to be elucidated. We previously developed an indicator system that
enabled detection of XBP1 splicing using fluorescent proteins as the reporter
signals. Here, we use a modification of this method that employs modified ER
stress-indicators and mutant IRE1 in vivo and in vitro to analyze XBP1
splicing mechanisms. Our analyses suggest that the 506–579nt region of the
XBP1 mRNA is necessary and sufficient for XBP1 splicing, that XBP1 splicing
can occur in the cytoplasm, and that cleavage and ligation of XBP1 mRNA
during splicing may occur as a coupled reaction.
}
}
@article{Zhang_Lin_Yao_Cai_Chen_Aierken_Wang_Song_2023,
title = {
XBP1 splicing contributes to endoplasmic reticulum stress-induced human islet
amyloid polypeptide up-regulation
},
author = {
Zhang, Yun and Lin, Susan and Yao, Jing and Cai, Wantong and Chen, Huaqiu and
Aierken, Ailikemu and Wang, Zhe and Song, Weihong
},
year = 2023,
month = oct,
journal = {Genes & Diseases},
volume = 11,
number = 5,
pages = 101148,
doi = {10.1016/j.gendis.2023.101148},
issn = {2352-4820},
abstractnote = {
As a pathological hallmark of type 2 diabetes mellitus (T2DM), islet amyloid
is formed by the aggregation of islet amyloid polypeptide (IAPP). Endoplasmic
reticulum (ER) stress interacts with IAPP aggregates and has been implicated
in the pathogenesis of T2DM. To examine the role of ER stress in T2DM, we
cloned the hIAPP promoter and analyzed its promoter activity in human
β-cells. We found that ER stress significantly enhanced hIAPP promoter
activity and expression in human β-cells via triggering X-box binding protein
1 (XBP1) splicing. We identified a binding site of XBP1 in the hIAPP
promoter. Disruption of this binding site by substitution or deletion
mutagenesis significantly diminished the effects of ER stress on hIAPP
promoter activity. Blockade of XBP splicing by MKC3946 treatment inhibited ER
stress-induced hIAPP up-regulation and improved human β-cell survival and
function. Our study uncovers a link between ER stress and IAPP at the
transcriptional level and may provide novel insights into the role of ER
stress in IAPP cytotoxicity and the pathogenesis of T2DM.
}
}
@article{wei_lung_2023,
title = {
Lung {SORT} {LNPs} enable precise homology-directed repair mediated
{CRISPR}/{Cas} genome correction in cystic fibrosis models
},
author = {
Wei, Tuo and Sun, Yehui and Cheng, Qiang and Chatterjee, Sumanta and Traylor,
Zachary and Johnson, Lindsay T. and Coquelin, Melissa L. and Wang, Jialu and
Torres, Michael J. and Lian, Xizhen and Wang, Xu and Xiao, Yufen and Hodges,
Craig A. and Siegwart, Daniel J.
},
year = 2023,
month = nov,
journal = {Nature Communications},
volume = 14,
number = 1,
pages = 7322,
doi = {10.1038/s41467-023-42948-2},
issn = {2041-1723},
url = {https://www.nature.com/articles/s41467-023-42948-2},
urldate = {2024-04-16},
copyright = {2023 The Author(s)},
note = {Publisher: Nature Publishing Group},
abstract = {
Approximately 10\% of Cystic Fibrosis (CF) patients, particularly those with
CF transmembrane conductance regulator (CFTR) gene nonsense mutations, lack
effective treatments. The potential of gene correction therapy through
delivery of the CRISPR/Cas system to CF-relevant organs/cells is hindered by
the lack of efficient genome editor delivery carriers. Herein, we report
improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for
efficient delivery of Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling
precise homology-directed repair-mediated gene correction in CF models.
Optimized Lung SORT LNPs deliver mRNA to lung basal cells in Ai9 reporter
mice. SORT LNP treatment successfully corrected the CFTR mutations in
homozygous G542X mice and in patient-derived human bronchial epithelial cells
with homozygous F508del mutations, leading to the restoration of CFTR protein
expression and chloride transport function. This proof-of-concept study will
contribute to accelerating the clinical development of mRNA LNPs for CF
treatment through CRISPR/Cas gene correction.
},
language = {en},
keywords = {Biomedical engineering, CRISPR-Cas9 genome editing, Gene delivery}
}
8:
@article{IBRAHIM2022215,
title = {
Polyethylene glycol (PEG): The nature, immunogenicity, and role in the
hypersensitivity of PEGylated products
},
author = {
Mohamed Ibrahim and Eslam Ramadan and Nehal E. Elsadek and Sherif E. Emam and
Taro Shimizu and Hidenori Ando and Yu Ishima and Omar Helmy Elgarhy and Hatem
A. Sarhan and Amal K. Hussein and Tatsuhiro Ishida
},
year = 2022,
journal = {Journal of Controlled Release},
volume = 351,
pages = {215--230},
doi = {https://doi.org/10.1016/j.jconrel.2022.09.031},
issn = {0168-3659},
url = {https://www.sciencedirect.com/science/article/pii/S0168365922006265},
keywords = {
Polyethylene glycol (PEG), anti-PEG antibodies, Hypersensitivity, COVID-19
mRNA vaccines, complement activation-related pseudoallergy (CARPA)
},
abstract = {
Polyethylene glycol (PEG) is a versatile polymer that is widely used as an
additive in foods and cosmetics, and as a carrier in PEGylated therapeutics.
Even though PEG is thought to be less immunogenic, or perhaps even
non-immunogenic, with a variety of physicochemical properties, there is
mounting evidence that PEG causes immunogenic responses when conjugated with
other materials such as proteins and nanocarriers. Under these conditions,
PEG with other materials can result in the production of anti-PEG antibodies
after administration. The antibodies that are induced seem to have a
deleterious impact on the therapeutic efficacy of subsequently administered
PEGylated formulations. In addition, hypersensitivity to PEGylated
formulations could be a significant barrier to the utility of PEGylated
products. Several reports have linked the presence of anti-PEG antibodies to
incidences of complement activation-related pseudoallergy (CARPA) following
the administration of PEGylated formulations. The use of COVID-19 mRNA
vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs),
has recently gained wide acceptance, although many cases of post-vaccination
hypersensitivity have been documented. Therefore, our review focuses not only
on the importance of PEGs and its great role in improving the therapeutic
efficacy of various medications, but also on the hypersensitivity reactions
attributed to the use of PEGylated products that include PEG-based mRNA
COVID-19 vaccines.
}
}
9:
@article{jiang_combinatorial_2024,
title = {
Combinatorial development of nebulized {mRNA} delivery formulations for the
lungs
},
author = {
Jiang, Allen Y. and Witten, Jacob and Raji, Idris O. and Eweje, Feyisayo and
MacIsaac, Corina and Meng, Sabrina and Oladimeji, Favour A. and Hu, Yizong
and Manan, Rajith S. and Langer, Robert and Anderson, Daniel G.
},
year = 2024,
month = mar,
journal = {Nature Nanotechnology},
volume = 19,
number = 3,
pages = {364--375},
doi = {10.1038/s41565-023-01548-3},
issn = {1748-3387, 1748-3395},
url = {https://www.nature.com/articles/s41565-023-01548-3},
urldate = {2024-09-10},
language = {en}
}
10:
@article{vila-gonzalez_vitro_2024,
title = {
In vitro platform to model the function of ionocytes in the human airway
epithelium
},
author = {
Vilà-González, Marta and Pinte, Laetitia and Fradique, Ricardo and Causa,
Erika and Kool, Heleen and Rodrat, Mayuree and Morell, Carola Maria and
Al-Thani, Maha and Porter, Linsey and Guo, Wenrui and Maeshima, Ruhina and
Hart, Stephen L. and McCaughan, Frank and Granata, Alessandra and Sheppard,
David N. and Floto, R. Andres and Rawlins, Emma L. and Cicuta, Pietro and
Vallier, Ludovic
},
year = 2024,
month = apr,
journal = {Respiratory Research},
volume = 25,
number = 1,
pages = 180,
doi = {10.1186/s12931-024-02800-7},
issn = {1465-993X},
url = {
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02800-7
},
urldate = {2024-09-10},
abstract = {
Background Pulmonary ionocytes have been identified in the airway epithelium
as a small population of ion transporting cells expressing high levels of
CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated
in cystic fibrosis. By providing an infinite source of airway epithelial
cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could
overcome some challenges of studying ionocytes. However, the production of
AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we
present a platform to produce hiPSCderived AECs (hiPSC-AECs) including
ionocytes and investigate their role in the airway epithelium.
Methods hiPSCs were differentiated into lung progenitors, which were
expanded as 3D organoids and matured by air-liquid interface culture as
polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a
hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for
ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their
wild-type (WT) isogenic controls were investigated by assessing gene and
protein expression, epithelial composition, cilia coverage and motility, pH
and transepithelial barrier properties.
Results Mature hiPSC-AEC epithelia contained basal cells, secretory cells,
ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and
ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of
their capacity to differentiate into airway progenitors. However, FOXI1 KO
led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to
produce ciliated cells.
Conclusion Our results suggest that ionocytes could have role beyond
transepithelial ion transport by regulating epithelial properties and
homeostasis in the airway epithelium.
},
language = {en}
}
11:
@book{book,
title = {Genome Editing and Biological Weapons: Assessing the Risk of Misuse},
author = {Paris, Katherine},
year = 2023,
month = {01},
publisher = {Springer Nature Switzerland AG},
pages = {},
doi = {10.1007/978-3-031-21820-0},
isbn = {978-3-031-21819-4}
}
12:
@article{wickiser2020biosecurity,
title = {
The democratization of biology: how CRISPR and synthetic biology usher in new
biosecurity threats
},
author = {Wickiser, Jason K., et al.},
year = 2020,
journal = {Defense Horizons},
volume = 85,
pages = {1--16},
url = {
https://ndupress.ndu.edu/Media/News/News-Article-View/Article/2386026/democratization-of-biology-crispr-synthetic-biology-new-biosecurity-threats/
}
}
13:
@article{cohen2019security,
title = {
Security implications of CRISPR-enabled genome editing: New weapons of mass
disruption?
},
author = {Cohen, Jon and Desai, Tej},
year = 2019,
journal = {Journal of Bioethical Inquiry},
publisher = {Springer},
volume = 16,
number = 2,
pages = {219--228},
doi = {10.1007/s11673-019-09914-5},
url = {https://doi.org/10.1007/s11673-019-09914-5}
}
14:
@article{doudna2020synthetic,
title = {
The rise of synthetic biology: New biosecurity risks and regulatory
challenges
},
author = {Doudna, Jennifer A. and Charpentier, Emmanuelle},
year = 2020,
journal = {Nature Reviews Genetics},
publisher = {Nature},
volume = 21,
number = 3,
pages = {144--156},
doi = {10.1038/s41576-019-0182-7},
url = {https://www.nature.com/articles/s41576-019-0182-7}
}
15:
@article{shwartz2019public,
title = {
Public perception of CRISPR and genome editing: Misconceptions and media
portrayal
},
author = {Shwartz, Mark and Conklin, Brian},
year = 2019,
journal = {Journal of Science Communication},
volume = 18,
number = 4,
pages = {A02},
doi = {10.22323/2.18040202},
url = {https://jcom.sissa.it/archive/18/04/JCOM_1804_2019_A02}
}
16:
@book{Chadwick_2012,
title = {Encyclopedia of applied ethics},
author = {Chadwick, Ruth F.},
year = 2012,
publisher = {Academic Press},
address = {London},
isbn = {978-0-12-373932-2},
edition = {2nd ed},
language = {eng}
}
17:
@article{Rubeis_Steger_2018,
title = {Risks and benefits of human germline genome editing: An ethical analysis},
author = {Rubeis, Giovanni and Steger, Florian},
year = 2018,
month = jul,
journal = {Asian Bioethics Review},
volume = 10,
number = 2,
pages = {133–141},
doi = {10.1007/s41649-018-0056-x},
issn = {1793-8759, 1793-9453},
language = {en}
}
18:
@article{Ansah_2022,
title = {
Ethical Challenges and Controversies in the Practice and Advancement of Gene
Therapy
},
author = {Ansah, Emmanuel Owusu},
year = 2022,
month = aug,
journal = {Advances in Cell and Gene Therapy},
volume = 2022,
pages = {1–5},
doi = {10.1155/2022/1015996},
issn = {2573-8461},
rights = {https://creativecommons.org/licenses/by/4.0/},
abstractnote = {
One of the most important technologies in modern medicine is gene therapy,
which allows therapeutic genes to be introduced into cells of the body. The
approach involves genetics and recombinant DNA techniques that allow
manipulating vectors for delivery of exogenous material to target cells. The
efficacy and safety of the delivery system are a key step towards the success
of gene therapy. Somatic cell gene therapy is the easiest in terms of
technology and the least problematic in terms of ethics. Although genetic
manipulation of germline cells at the gene level has the potential to
permanently eradicate certain hereditary disorders, major ethical issues such
as eugenics, enhancement, mosaicism, and the transmission of undesirable
traits or side effects to patients’ descendants currently stymie its
development, leaving only somatic gene therapy in the works. However, moral,
social, and ethical arguments do not imply that germline gene therapy should
be banned forever. This review discusses in detail the current challenges
surrounding the practice of gene therapy, focusing on the moral arguments and
scientific claims that affect the advancement of the technology. The review
also suggests precautionary principles as a means to navigate ethical
uncertainties.
},
editor = {Miao, Carol H.},
language = {en}
}
19:
@book{Pugh_2020,
title = {Autonomy, Rationality, and Contemporary Bioethics},
author = {Pugh, Jonathan},
year = 2020,
month = apr,
publisher = {Oxford University PressOxford},
doi = {10.1093/oso/9780198858584.001.0001},
isbn = {978-0-19-885858-4},
url = {https://academic.oup.com/book/33778},
edition = 1,
rights = {https://creativecommons.org/licenses/by-nc-nd/4.0/},
abstractnote = {
Abstract Personal autonomy is often lauded as a key value in
contemporary Western bioethics, and the claim that there is an important
relationship between autonomy and rationality is often treated as an
uncontroversial claim in this sphere. Yet, there is also considerable
disagreement about how we should cash out the relationship between
rationality and autonomy. In particular, it is unclear whether a rationalist
view of autonomy can be compatible with legal judgments that enshrine a
patient’s right to refuse medical treatment, regardless of whether ‘… the
reasons for making the choice are rational, irrational, unknown or even
non-existent’. This book brings recent philosophical work on the nature of
rationality to bear on the question of how we should understand autonomy in
contemporary bioethics. In doing so, the author develops a new framework for
thinking about the concept, one that is grounded in an understanding of the
different roles that rational beliefs and rational desires have to play in
personal autonomy. Furthermore, the account outlined here allows for a deeper
understanding of different forms of controlling influence, and the
relationship between our freedom to act, and our capacity to decide
autonomously. The author contrasts his rationalist account with other
prominent accounts of autonomy in bioethics, and outlines the revisionary
implications it has for various practical questions in bioethics in which
autonomy is a salient concern, including questions about the nature of
informed consent and decision-making capacity.
},
language = {en}
}
20:
@inbook{Gstraunthaler_Lindl_2013,
title = {Allgemeine Aspekte der Primärkultur},
author = {Gstraunthaler, Gerhard and Lindl, Toni},
year = 2013,
booktitle = {Zell- und Gewebekultur: Allgemeine Grundlagen und spezielle Anwendungen},
publisher = {Springer},
address = {Berlin, Heidelberg},
pages = {151–162},
doi = {10.1007/978-3-642-35997-2_16},
isbn = {978-3-642-35997-2},
url = {https://doi.org/10.1007/978-3-642-35997-2_16},
abstractnote = {
Definitionsgemäß versteht man unter Primärkultur alle In-vitro-Züchtungen von
Zellen, Geweben und Organen, die direkt aus dem Organismus entnommen wurden.
Wird diese Erstkultur weiter subkultiviert, spricht man von einer
Sekundärkultur und in weiterer Folge bereits von einer Zelllinie (Schaeffer,
1990) (Abb. 16-1). In den meisten Fällen kann eine Primärkultur nicht mehr
weitergezüchtet werden (Abschn. 16.2). Während eine Organkultur nicht in
ihrer Struktur- und Organisationseinheit zerstört werden soll (Kap. 23), ist
die Gewebekultur von einer mehr oder minder starken Desintegration aus einem
Organismus abhängig. Für die Gewinnung einer Zellkultur ist eine vollständige
Dissoziation des Gewebes bzw. des Organs in Einzelzellen notwendig.
},
editor = {Gstraunthaler, Gerhard and Lindl, Toni},
language = {de}
}
21:
@book{book1,
author = {Thiele, F.},
year = 2001,
booktitle = {International Encyclopedia of the Social & Behavioral Sciences},
publisher = {Elsevier},
pages = {13224–13227},
doi = {10.1016/B0-08-043076-7/00191-1},
isbn = {978-0-08-043076-8},
url = {https://linkinghub.elsevier.com/retrieve/pii/B0080430767001911},
rights = {https://www.elsevier.com/tdm/userlicense/1.0/},
language = {en}
}
22:
@inbook{Gethmann_2001,
title = {Research: Ethical Aspects of Long-term Responsibilities},
author = {Gethmann, C.F.},
year = 2001,
booktitle = {International Encyclopedia of the Social & Behavioral Sciences},
publisher = {Elsevier},
pages = {13227–13231},
doi = {10.1016/B0-08-043076-7/00159-5},
isbn = {978-0-08-043076-8},
url = {https://linkinghub.elsevier.com/retrieve/pii/B0080430767001595},
rights = {https://www.elsevier.com/tdm/userlicense/1.0/},
language = {en}
}
23:
@article{Kiani_Pheby_Henehan_Brown_Sieving_Sykora_Marks_Falsini_Capodicasa_Miertus_et,
title = {Ethical considerations regarding animal experimentation},
author = {
Kiani, Aysha Karim and Pheby, Derek and Henehan, Gary and Brown, Richard and
Sieving, Paul and Sykora, Peter and Marks, Robert and Falsini, Benedetto and
Capodicasa, Natale and Miertus, Stanislav and Lorusso, Lorenzo and
Dondossola, Daniele and Tartaglia, Gianluca Martino and Ergoren, Mahmut
Cerkez and Dundar, Munis and Michelini, Sandro and Malacarne, Daniele and
Bonetti, Gabriele and Dautaj, Astrit and Donato, Kevin and Medori, Maria
Chiara and Beccari, Tommaso and Samaja, Michele and Connelly, Stephen
Thaddeus and Martin, Donald and Morresi, Assunta and Bacu, Ariola and Herbst,
Karen L. and Kapustin, Mykhaylo and Stuppia, Liborio and Lumer, Ludovica and
Farronato, Giampietro and Bertelli, Matteo and INTERNATIONAL BIOETHICS STUDY
GROUP
},
year = 2022,
month = jun,
journal = {Journal of Preventive Medicine and Hygiene},
volume = 63,
number = {2 Suppl 3},
pages = {E255–E266},
doi = {10.15167/2421-4248/jpmh2022.63.2S3.2768},
issn = {2421-4248},
abstractnote = {
Animal experimentation is widely used around the world for the identification
of the root causes of various diseases in humans and animals and for
exploring treatment options. Among the several animal species, rats, mice and
purpose-bred birds comprise almost 90% of the animals that are used for
research purpose. However, growing awareness of the sentience of animals and
their experience of pain and suffering has led to strong opposition to animal
research among many scientists and the general public. In addition, the
usefulness of extrapolating animal data to humans has been questioned. This
has led to Ethical Committees’ adoption of the “four Rs” principles
(Reduction, Refinement, Replacement and Responsibility) as a guide when
making decisions regarding animal experimentation. Some of the essential
considerations for humane animal experimentation are presented in this review
along with the requirement for investigator training. Due to the ethical
issues surrounding the use of animals in experimentation, their use is
declining in those research areas where alternative in vitro or in silico
methods are available. However, so far it has not been possible to dispense
with experimental animals completely and further research is needed to
provide a road map to robust alternatives before their use can be fully
discontinued.
},
language = {eng}
}