The Code Breaker: Jennifer Doudna, gene editing, and the future of the human race

2021 ◽  
Vol 26 (2) ◽  
Author(s):  
Arthur A Boni
Keyword(s):  
Technology Transfer ◽  
Business Model ◽  
High Performance ◽  
Gene Editing ◽  
Team Building ◽  
Human Race ◽  
Academic Scientist ◽  
Biotechnology Companies ◽  
Academic Laboratory

In this book review and accompanying commentary and Addendum, we focus on 5 principal topics/major themes that are of interest for our readership, with a focus on framing the translation of transformative technology into a platform business model in biopharma.  We focus on: 1) the behavioral and personal side of the story of the academic scientist, in this case the principal “code breaker” – Jennifer Doudna; 2) the innovation/technology transfer models, including team building appropriate for successfully translating technology from the academic laboratory into the private sector; 3) the IP considerations needed for broad commercialization and dissemination of pivotal, platform inventions in biopharma; and, 4) framing the issues surrounding the ethical discussion related to use in patients associated with a transformative, gene based technology like CRISPR. We also include an Addendum that covers, 5) Some pertinent, concluding comments on the importance of high–performance, diverse teams for founding, building, and growing successful biotechnology companies.

Guidelines for Delivering Personal-Disclosure Mutual-Sharing Team Building Interventions

2006 ◽  
Vol 20 (3) ◽  
pp. 348-367 ◽  
Author(s):  
Nicholas L. Holt ◽  
John G.H. Dunn
Keyword(s):  
High Performance ◽  
Group Communication ◽  
Team Building ◽  
Contextual Sensitivity ◽  
Communication Practices ◽  
Soccer Team ◽  
Building Activities ◽  
Professional Guidance ◽  
Personal Disclosure ◽  
Women's Soccer

The overall purpose of this study was to provide professional guidance to practitioners who may wish to deliver Personal-Disclosure Mutual-Sharing (PDMS) team building activities. First we replicated and evaluated a PDMS intervention previously used by Dunn and Holt (2004). Fifteen members (M age = 25.4 yrs) of a high performance women’s soccer team provided evaluative data about the intervention they received via reflective interviews. Benefits of the PDMS activity were enhanced understanding, increased cohesion, and improved confidence. Guidelines for professionals who may wish to use this team building approach are provided in terms of (a) establishing group communication practices during the season, (b) delivering the meeting, and (c) demonstrating contextual sensitivity.

scholarly journals Time for a new business model?

1969 ◽  
Vol 16 (1) ◽  
Author(s):  
Yali Friedman
Keyword(s):  
Business Model ◽  
Hybrid Model ◽  
Business Models ◽  
The United States ◽  
Biotechnology Industry ◽  
New Firms ◽  
Technology Platform ◽  
Economic Climate ◽  
New Business ◽  
Biotechnology Companies

In the relatively short history of the biotechnology industry, new business models have emerged every few years. Some have been little more than short-lived marketing or investment-attraction devices, whereas others have had endured as viable options. Given the dramatic changes in the economic climate and potentially the regulations affecting biotechnology, is it time for a new business model?A SHORT HISTORYFirst there was the FILCO, or fully integrated life science company, business model. This model, employed by some of the first biotechnology companies, positioned firms to capture the revolutionary advances of biotechnology and to build large vertically-integrated companies. Companies like Amgen and Genentech were able to fulfill this endpoint, but many other companies were not so fortunate. Another early model was to improve existing products, rather than to build an entire franchise around discovering and commercializing new ones. This model is exemplified by Alza, which was founded to improve medical treatment through controlled drug delivery and focused on improving existing drugs rather than developing new ones. This same model is still employed today, and shares some similarity with the technology platform business model, where companies focus on developing technologies that can be sold to other R&D firms, rather than independently developing consumer applications.Newer business models did not replace the older ones, but rather enabled new firms to focus on the unique environment in which they were founded. Examples include the hybrid model that combined product development with a technology platform, which could be sold or licensed to others, and the no research, development-only model that as a derivative of the specialty pharmaceutical model, saw newly founded companies buying drug leads off of other companies to complete late-stage clinical trials. These models enabled new firms to meet the respective needs of risk-averse and cash-rich investors.WHERE ARE WE NOW?I've previously written that the global economic crisis has been (and still is) transformative for the biotechnology industry. The aforementioned biotechnology business models rose to prominence in conditions that favored them. For example, the hybrid model emerged in a funding drought and was favored as it enabled companies to build internal revenue streams while still maintaining the possibility to realize the upside of product sales.What are the factors influencing biotechnology companies today? In the United States, beyond the general economic climate there are still unresolved questions about the availability of early stage financing, the ability to recruit foreign workers, and – post-commercialization – data exclusivity, generic biologics and the potential for price controls. Internationally, some nations are still undergoing dramatic economic reorganizations, while others are making significant investments in building biotechnology R&D capacity.So, the question remains: Is the biotechnology industry ready for a new business model, and is there a business model that can accommodate the myriad domestic challenges faced by many countries while addressing the increasing globalization of activities?

scholarly journals Adenine Base Editing of the Sickle Allele in CD34+ Hematopoietic Stem and Progenitor Cells Eliminates Hemoglobin S

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-47
Author(s):  
S. Haihua Chu ◽  
Daisy Lam ◽  
Michael S. Packer ◽  
Jennifer Olins ◽  
Alexander Liquori ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Base Pair ◽  
High Performance ◽  
Gene Editing ◽  
Publicly Traded ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Adenine Base

While there are several small molecule, gene therapy, and gene editing approaches for treating sickle cell disease (SCD), these strategies do not result in the direct elimination of the causative sickle β-globin (HbS) variant itself. The reduction or complete removal of this pathologic globin variant and expression of normal β-hemoglobin (HbB) or other non-polymerizing β-globin variant may increase the likelihood of beneficial outcomes for SCD patients. Adenine base editors (ABEs) can precisely convert the mutant A-T base pair responsible for SCD to a G-C base pair, thus generating the hemoglobin variant, Hb G-Makassar, a naturally occurring β-globin variant that is not associated with human disease. Our studies have identified ABEs that can achieve highly efficient Makassar editing (>70%) of the sickle mutation in both sickle trait (HbAS) and homozygous sickle (HbSS) patient CD34+ cells with high cell viability and recovery and without perturbation of immunophenotypic hematopoietic stem and progenitor cell (HSPC) frequencies after ex vivo delivery of guide RNA and mRNA encoding the ABE. Furthermore, Makassar editing was retained throughout erythropoiesis in bulk in vitro erythroid differentiated cells (IVED) derived from edited CD34+ cells. To gain an understanding of allelic editing at a single clone resolution, we assessed editing frequencies of clones from both single cell expansion in erythroid differentiation media, as well as from single BFU-E colonies. We found that we could achieve >70% of colonies with bi-allelic Makassar editing and approximately 20% of colonies with mono-allelic Makassar editing, while <3% of colonies remained completely unedited. Previously, conventional hemoglobin capillary electrophoresis and high-performance liquid chromatography (HPLC) were unable to distinguish between HbS and HbG-Makassar. Here, we developed an ultra-high-performance liquid chromatography (UPLC) method that resolves sickle globin (HbS) from Hb G-Makassar globin in IVED cells. The Makassar globin variant was further confirmed by liquid chromatography mass spectrometry (LC-MS). By developing this new method to resolve these two β-globin variants in edited HbSS cells, we were able to detect, in bulk IVED cultures, >80% abundance Hb G-Makassar of total β-globins, which corresponded to a concomitant reduction of HbS levels to <20%. Furthermore, we were also able to determine globin abundance as well as allelic editing at the level of single clones and found that HbS was completely eliminated in >70% of cells that had bi-allelic Makassar editing. Moreover, in the approximately 20% of colonies that were found to be mono-allelically edited for the Makassar variant, there was a 60:40 ratio of Hb G-Makassar:HbS globin abundance in individual clones, at levels remarkably similar to the HbA(wildtype HbB):HbS levels found in HbAS individuals, with minimal observable in vitro sickling when exposed to hypoxia. Thus, with our ABEs, we were able to reduce HbS to <40% on a per cell basis in >90% of IVED cells and found that in vitro sickling under hypoxia inversely correlated with the level of Hb G-Makassar globin variant installation and corresponding reduction in HbS levels. By converting HbS to Hb G-Makassar, our direct and precise editing strategy replaces a pathogenic β-globin with one that has been shown to have normal hematologic parameters. Coupled with autologous stem cell transplant, this next generation gene editing strategy presents a promising new modality for treating patients with SCD. Disclosures Chu: Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lam:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Packer:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Olins:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Liquori:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Marshall:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lee:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Yan:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Decker:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gantzer:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Haskett:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Bohnuud:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Born:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Barrera:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Slaymaker:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gaudelli:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Hartigan:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company. Ciaramella:Beam Therapeutics: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Establishing an academic laboratory: mentoring as a business model

2014 ◽  
Vol 25 (21) ◽  
pp. 3251-3253 ◽  
Author(s):  
Valentina Greco
Keyword(s):  
Business Model ◽  
Cell Biology ◽  
Critical Components ◽  
Academic Laboratory ◽  
To Receive

It is a tremendous honor for my group and me to receive the recognition of the 2014 Women in Cell Biology Junior Award. I would like to take the opportunity of this essay to describe my scientific journey, discuss my philosophy about running a group, and propose what I think is a generalizable model to efficiently establish an academic laboratory. This essay is about my view on the critical components that go into establishing a highly functional academic laboratory during the current tough, competitive times.

Your winning business model agenda: four questions to shape growth

2018 ◽  
Vol 46 (4) ◽  
pp. 21-27 ◽  
Author(s):  
Vladyslav Biloshapka ◽  
Oleksiy Osiyevskyy
Keyword(s):  
Business Model ◽  
High Performance ◽  
Design Methodology ◽  
Business Models ◽  
Scale Up ◽  
The Other ◽  
Content Type ◽  
Current State ◽  
Growth Planning ◽  
Practical Implications

Purpose Defines clear steps for growth planning that support answers to the crucial question: How and where are you planning to scale up the business and what talent do you need to implement this? Design/methodology/approach As the “Business model value matrix” shows, having ‘happy customers’ is only one determinant of a business model’s success. The other essential block of diagnostic questions deals with the current state and prospects of the firm’s growth. Findings We found that companies that have found ways to keep their business models in a winner’s state can provide clear, evidence-based answers to questions about growth opportunities and risks, while their less successful peers have difficulty addressing the issues. Continuous collecting and analyzing of this information allows successful companies to embrace the strategy-as-learning model of development, built around active learning and proactive adjustment to evolving environment. Practical implications To develop a strategy for moving to and sustaining the Winner state, managers must clearly articulate and test a set of hypotheses about the mechanisms of their company’s growth. The first step on this path is related to obtaining a clear view on the factors that underpin the current financial performance. Originality/value High-performance cultures make sure that each manager has the clear answers to the questions of value, growth and digitization in order to learn, experiment and implement the company business model agenda. The unproductive cultures, on the other hand, are sustained by managerial teams that usually do not have the answers to these crucial questions, but are very good at political games.

CRISPR/Cas9-induced β-carotene Hydroxylase Mutation in Dunaliella Salina CCAP19/18

2021 ◽  
Author(s):  
Lina Hu ◽  
Shu ying FENG ◽  
Gaofeng Liang ◽  
Jingxia Du ◽  
Aifang Li ◽  
...  
Keyword(s):  
High Performance ◽  
Dunaliella Salina ◽  
Gene Editing ◽  
Expression System ◽  
Transformation Method ◽  
Practical Significance ◽  
Exon 1 ◽  
Targeted Gene Editing ◽  
Foreign Genes ◽  
Β Carotene

Abstract Dunaliella salina (D. salina) has been exploited as a novel expression system for the field of genetic engineering. However, owing to the low or inconsistent expression of target proteins, it has been greatly restricted to practical production of recombinant proteins. Since the accurate gene editing function of CRISPR/Cas system, β-carotene hydroxylase gene was chosen as an example to explore D. salina application with the purpose of improving expression level of foreign genes. In this paper, based on pKSE401 backbone, three CRISPR/Cas9 binary vectors were constructed to targeting exon 1 and 3 of the β-carotene hydroxylase of D. salina CCAP19/18 (Dschyb). D. salina mutants were obtained by salt gradient transformation method, and the expression of Dschyb gene were identified through real-time fluorescent quantitative PCR. Moreover, carotenoids content was analyzed by high-performance liquid chromatography at different time points after high intensity treatment. Compared with wild type strains, the β-carotene levels of mutants showed a significant increase, nearly up to 1.4 μg/ml, and the levels of zeaxanthin decreased to various degrees in mutants. All the results provide a compelling evidence for targeted gene editing in D. salina. This study gave a first successful gene editing of D. salina which has a very important practical significance for increasing carotene yield and meeting realistic industry demand. Furthermore, it provides an approach to overcome the current obstacles of D. salina, and then gives a strong tool to facilitates the development and application of D. salina system.

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