Human germline gene modification: a dissent

Billings, Paul R.; Hubbard, R. Glenn; Newman, Stuart A.

doi:10.1016/s0140-6736(99)01173-3

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…Third, improved cell targeting establishes an important principle by which accidental transduction of germ cells can be avoided. Although this constitutes a rather theoretical risk, every form of a preventive action is certainly welcome (Billings et al, 1999). Fourth, cell-specific targeting, or the use of envelopes that are recognized by preformed antibodies, should increase biosafety in the case of vector shedding.…”

Section: Pseudotypes Targeting and Sheddingmentioning

confidence: 99%

Biosafety Features of Lentiviral Vectors

et al. 2013

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Over the past decades, lentiviral vectors have evolved as a benchmark tool for stable gene transfer into cells with a high replicative potential. Their relatively flexible genome and ability to transduce many forms of nondividing cells, combined with the potential for cell-specific pseudotyping, provides a rich resource for numerous applications in experimental platforms and therapeutic settings. Here, we give an overview of important biosafety features of lentiviral vectors, with detailed discussion of (i) the principles of the lentiviral split-genome design used for the construction of packaging cells; (ii) the relevance of modifications introduced into the lentiviral long terminal repeat (deletion of enhancer/promoter sequences and introduction of insulators); (iii) the basic features of mRNA processing, including the Rev/Rev-responsive element (RRE) interaction and the modifications of the 3' untranslated region of lentiviral vectors with various post-transcriptional regulatory elements affecting transcriptional termination, polyadenylation, and differentiation-specific degradation of mRNA; and (iv) the characteristic integration pattern with the associated risk of transcriptional interference with cellular genes. We conclude with considerations regarding the importance of cell targeting via envelope modifications. Along this course, we address canonical biosafety issues encountered with any type of viral vector: the risks of shedding, mobilization, germline transmission, immunogenicity, and insertional mutagenesis.

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Section: Pseudotypes Targeting and Sheddingmentioning

confidence: 99%

Biosafety Features of Lentiviral Vectors

et al. 2013

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“…The debate seeks to reconcile scientifically and ethically justified concern about certain potential dangers of germline gene editing—such as unforeseen side effects,20 62 lack of future children's informed consent20 62 and, of course, detrimental eugenics23—with the need to foster rigorous research and eventual application of CRISPR to somatic cells in order to eradicate individuals' genetic diseases. With respect to germline gene editing, several countries, including Canada and Mexico, already have a legislative ban, while others, including China and India, have instituted bans within guidelines, which carry less force than legislation 63.…”

Section: Resultsmentioning

confidence: 99%

Everything in moderation, even hype: learning from vaccine controversies to strike a balance with CRISPR

Benston

2017

J Med Ethics

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The ease and applicability of CRISPR/Cas9—a new and precise gene-editing and reproductive technology—have garnered hype and heightened concern about its potential “unprecedented and horrific consequences” and have led many scientific leaders to call for a moratorium on its research and use. CRISPR appears distinctly more controversial than previous technological innovations (genetic or otherwise), with a greater reach and speed of human treatment and enhancement; however, we have seen similarly inflated hopes and fears in response to other medical innovations for well over a century. One intervention that has both historically and recently incited alarm—vaccines—serves as a pertinent example of what could go wrong if a technology’s reach is shortened due to inflated fears. By comparing the vaccine controversy and the CRISPR debate, we can help separate the hype from the realistic potential of these technologies. How our society grapples with such innovations will determine the extent to which their impact on our individual and collective health will be beneficial. We must recognize the need for a tempered approach to CRISPR conversation leading to regulation and ethical application. Although CRISPR’s reach will continue expanding with ongoing research, thus requiring continuous evaluation, the lessons we’ve learned from the vaccine controversy demonstrate that our approach must not be to shut down regulation and application now, but to thoughtfully conjoin productive debate and action so that therapeutic gene-editing can alleviate suffering as soon as possible without precipitating social outcomes we would belatedly deplore.

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“…It is possible to conceive that such technology may promise the possibility of correcting the affected coagulation factor gene in the germline of haemophilic patients and so ‘prevent’ haemophilia in future generations. Although perhaps an unrealistic goal at present, the ethics of these potential aspects of gene therapy need to be fully and widely debated, as they have wide implications for genetic manipulation in general (Billings et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

Gene therapy for haemophilia

Pasi

2001

Br J Haematol

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Human germline gene modification: a dissent

Cited by 17 publications

References 21 publications

Biosafety Features of Lentiviral Vectors

Biosafety Features of Lentiviral Vectors

Everything in moderation, even hype: learning from vaccine controversies to strike a balance with CRISPR

Gene therapy for haemophilia

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