Posts Tagged ‘Nature’

Multiple Major Scientific Journals Will Fully Adopt Open Access Under Plan S

Curator: Stephen J. Williams, PhD

More university library systems have been pressuring major scientific publishing houses to adopt an open access strategy in order to reduce the library system’s budgetary burdens.  In fact some major universities like the California system of universities (University of California and other publicly funded universities in the state as well as Oxford University in the UK, even MIT have decided to become their own publishing houses in a concerted effort to fight back against soaring journal subscription costs as well as the costs burdening individual scientists and laboratories (some of the charges to publish one paper can run as high as $8000.00 USD while the journal still retains all the rights of distribution of the information).  Therefore more and more universities, as well as concerted efforts by the European Union and the US government are mandating that scientific literature be published in an open access format.

The results of this pressure are evident now as major journals like Nature, JBC, and others have plans to go fully open access in 2021.  Below is a listing and news reports of some of these journals plans to undertake a full Open Access Format.


Nature to join open-access Plan S, publisher says

09 APRIL 2020 UPDATE 14 APRIL 2020

Springer Nature says it commits to offering researchers a route to publishing open access in Nature and most Nature-branded journals from 2021.

Richard Van Noorden

After a change in the rules of the bold open-access (OA) initiative known as Plan S, publisher Springer Nature said on 8 April that many of its non-OA journals — including Nature — were now committed to joining the plan, pending discussion of further technical details.

This means that Nature and other Nature-branded journals that publish original research will now look to offer an immediate OA route after January 2021 to scientists who want it, or whose funders require it, a spokesperson says. (Nature is editorially independent of its publisher, Springer Nature.)

“We are delighted that Springer Nature is committed to transitioning its journals to full OA,” said Robert Kiley, head of open research at the London-based biomedical funder Wellcome, and the interim coordinator for Coalition S, a group of research funders that launched Plan S in 2018.

But Lisa Hinchliffe, a librarian at the University of Illinois at Urbana–Champaign, says the changed rules show that publishers have successfully pushed back against Plan S, softening its guidelines and expectations — in particular in the case of hybrid journals, which publish some content openly and keep other papers behind paywalls. “The coalition continues to take actions that rehabilitate hybrid journals into compliance rather than taking the hard line of unacceptability originally promulgated,” she says.





What is Plan S?

The goal of Plan S is to make scientific and scholarly works free to read as soon as they are published. So far, 17 national funders, mostly in Europe, have joined the initiative, as have the World Health Organization and two of the world’s largest private biomedical funders — the Bill & Melinda Gates Foundation and Wellcome. The European Commission will also implement an OA policy that is aligned with Plan S. Together, this covers around 7% of scientific articles worldwide, according to one estimate. A 2019 report published by the publishing-services firm Clarivate Analytics suggested that 35% of the research content published in Nature in 2017 acknowledged a Plan S funder (see ‘Plan S papers’).


Journal Total papers in 2017 % acknowledging Plan S funder
Nature 290 35%
Science 235 31%
Proc. Natl Acad. Sci. USA 639 20%

Source: The Plan S footprint: Implications for the scholarly publishing landscape (Institute for Scientific Information, 2019)


Source: https://www.nature.com/articles/d41586-020-01066-5

Opening ASBMB publications freely to all


Lila M. Gierasch, Editor-in-Chief, Journal of Biological Chemistry

Nicholas O. Davidson

Kerry-Anne Rye, Editors-in-Chief, Journal of Lipid Research and 

Alma L. Burlingame, Editor-in-Chief, Molecular and Cellular Proteomics


We are extremely excited to announce on behalf of the American Society for Biochemistry and Molecular Biology (ASBMB) that the Journal of Biological Chemistry (JBC), Molecular & Cellular Proteomics (MCP), and the Journal of Lipid Research (JLR) will be published as fully open-access journals beginning in January 2021. This is a landmark decision that will have huge impact for readers and authors. As many of you know, many researchers have called for journals to become open access to facilitate scientific progress, and many funding agencies across the globe are either already requiring or considering a requirement that all scientific publications based on research they support be published in open-access journals. The ASBMB journals have long supported open access, making the accepted author versions of manuscripts immediately and permanently available, allowing authors to opt in to the immediate open publication of the final version of their paper, and endorsing the goals of the larger open-access movement (1). However, we are no longer satisfied with these measures. To live up to our goals as a scientific society, we want to freely distribute the scientific advances published in JBC, MCP, and JLR as widely and quickly as possible to support the scientific community. How better can we facilitate the dissemination of new information than to make our scientific content freely open to all?

For ASBMB journals and others who have contemplated or made the transition to publishing all content open access, achieving this milestone generally requires new financial mechanisms. In the case of the ASBMB journals, the transition to open access is being made possible by a new partnership with Elsevier, whose established capabilities and economies of scale make the costs associated with open-access publication manageable for the ASBMB (2). However, we want to be clear: The ethos of ASBMB journals will not change as a consequence of this new alliance. The journals remain society journals: The journals are owned by the society, and all scientific oversight for the journals will remain with ASBMB and its chosen editors. Peer review will continue to be done by scientists reviewing the work of scientists, carried out by editorial board members and external referees on behalf of the ASBMB journal leadership. There will be no intervention in this process by the publisher.

Although we will be saying “goodbye” to many years of self-publishing (115 in the case of JBC), we are certain that we are taking this big step for all the right reasons. The goal for JBC, MCP, and JLR has always been and will remain to help scientists advance their work by rapidly and effectively disseminating their results to their colleagues and facilitating the discovery of new findings (13), and open access is only one of many innovations and improvements in science publishing that could help the ASBMB journals achieve this goal. We have been held back from fully exploring these options because of the challenges of “keeping the trains running” with self-publication. In addition to allowing ASBMB to offer all the content in its journals to all readers freely and without barriers, the new partnership with Elsevier opens many doors for ASBMB publications, from new technology for manuscript handling and production, to facilitating reader discovery of content, to deploying powerful analytics to link content within and across publications, to new opportunities to improve our peer review mechanisms. We have all dreamed of implementing these innovations and enhancements (45) but have not had the resources or infrastructure needed.

A critical aspect of moving to open access is how this decision impacts the cost to authors. Like most publishers that have made this transition, we have been extremely worried that achieving open-access publishing would place too big a financial burden on our authors. We are pleased to report the article-processing charges (APCs) to publish in ASBMB journals will be on the low end within the range of open-access fees: $2,000 for members and $2,500 for nonmembers. While slightly higher than the cost an author incurs now if the open-access option is not chosen, these APCs are lower than the current charges for open access on our existing platform.


1.↵ Gierasch, L. M., Davidson, N. O., Rye, K.-A., and Burlingame, A. L. (2019) For the sake of science. J. Biol. Chem. 294, 2976 FREE Full Text

2.↵ Gierasch, L. M. (2017) On the costs of scientific publishing. J. Biol. Chem. 292, 16395–16396 FREE Full Text

3.↵ Gierasch, L. M. (2020) Faster publication advances your science: The three R’s. J. Biol. Chem. 295, 672 FREE Full Text

4.↵ Gierasch, L. M. (2017) JBC is on a mission to facilitate scientific discovery. J. Biol. Chem. 292, 6853–6854 FREE Full Text

5.↵ Gierasch, L. M. (2017) JBC’s New Year’s resolutions: Check them off! J. Biol. Chem. 292, 21705–21706 FREE Full Text


Source: https://www.jbc.org/content/295/22/7814.short?ssource=mfr&rss=1


Open access publishing under Plan S to start in 2021


2019; 365 doi: https://doi.org/10.1136/bmj.l2382 (Published 31 May 2019)Cite this as: BMJ 2019;365:l2382

From 2021, all research funded by public or private grants should be published in open access journals, according to a group of funding agencies called coALition S.1

The plan is the final version of a draft that was put to public consultation last year and attracted 344 responses from institutions, almost half of them from the UK.2 The responses have been considered and some changes made to the new system called Plan S, a briefing at the Science Media Centre in London was told on 29 May.

The main change has been to delay implementation for a year, to 1 January 2021, to allow more time for those involved—researchers, funders, institutions, publishers, and repositories—to make the necessary changes, said John-Arne Røttingen, chief executive of the Research Council of Norway.

“All research contracts signed after that date should include the obligation to publish in an open access journal,” he said. T……

(Please Note in a huge bit of irony this article is NOT Open Access and behind a paywall…. Yes an article about an announcement to go Open Access is not Open Access)

Source: https://www.bmj.com/content/365/bmj.l2382.full



Plan S

From Wikipedia, the free encyclopedia

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Not to be confused with S-Plan.

Plan S is an initiative for open-access science publishing launched in 2018[1][2] by “cOAlition S”,[3] a consortium of national research agencies and funders from twelve European countries. The plan requires scientists and researchers who benefit from state-funded research organisations and institutions to publish their work in open repositories or in journals that are available to all by 2021.[4] The “S” stands for “shock”.[5]

Principles of the plan[edit]

The plan is structured around ten principles.[3] The key principle states that by 2021, research funded by public or private grants must be published in open-access journals or platforms, or made immediately available in open access repositories without an embargo. The ten principles are:

  1. authors should retain copyrighton their publications, which must be published under an open license such as Creative Commons;
  2. the members of the coalition should establish robust criteria and requirements for compliant open access journals and platforms;
  3. they should also provide incentives for the creation of compliant open access journals and platforms if they do not yet exist;
  4. publication fees should be covered by the funders or universities, not individual researchers;
  5. such publication fees should be standardized and capped;
  6. universities, research organizations, and libraries should align their policies and strategies;
  7. for books and monographs, the timeline may be extended beyond 2021;
  8. open archives and repositories are acknowledged for their importance;
  9. hybrid open-access journalsare not compliant with the key principle;
  10. members of the coalition should monitor and sanction non-compliance.

Member organisations

Organisations in the coalition behind Plan S include:[14]

International organizations that are members:

Plan S is also supported by:


Other articles on Open Access on this Open Access Journal Include:

MIT, guided by open access principles, ends Elsevier negotiations, an act followed by other University Systems in the US and in Europe


Open Access e-Scientific Publishing: Elected among 2018 Nature’s 10 Top Influencers – ROBERT-JAN SMITS: A bureaucrat launched a drive to transform science publishing


Electronic Scientific AGORA: Comment Exchanges by Global Scientists on Articles published in the Open Access Journal @pharmaceuticalintelligence.com – Four Case Studies


Mozilla Science Lab Promotes Data Reproduction Through Open Access: Report from 9/10/2015 Online Meeting


Elsevier’s Mendeley and Academia.edu – How We Distribute Scientific Research: A Case in Advocacy for Open Access Journals


The Fatal Self Distraction of the Academic Publishing Industry: The Solution of the Open Access Online Scientific Journals
PeerJ Model for Open Access Scientific Journal
“Open Access Publishing” is becoming the mainstream model: “Academic Publishing” has changed Irrevocably
Open-Access Publishing in Genomics













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Prime Editing as a New CRISPR Tool to Enhance Precision and Versatility


Reporter: Stephen J. Williams, PhD


CRISPR has become a powerful molecular for the editing of genomes tool in research, drug discovery, and the clinic

(see posts and ebook on this site below)


however, as discussed on this site

(see posts below)

there have been many instances of off-target effects where genes, other than the selected target, are edited out.  This ‘off-target’ issue has hampered much of the utility of CRISPR in gene-therapy and CART therapy

see posts


However, an article in Science by Jon Cohen explains a Nature paper’s finding of a new tool in the CRISPR arsenal called prime editing, meant to increase CRISPR specificity and precision editing capabilities.


By Jon Cohen | Oct 25th, 2019

Prime editing promises to be a cut above CRISPR Jon Cohen CRISPR, an extraordinarily powerful genome-editing tool invented in 2012, can still be clumsy. … Prime editing steers around shortcomings of both techniques by heavily modifying the Cas9 protein and the guide RNA. … ” Prime editing “well may become the way that disease-causing mutations are repaired,” he says.

Science Vol. 366, No. 6464; DOI: 10.1126/science.366.6464.406

The effort, led by Drs. David Liu and Andrew Anzalone at the Broad Institute (Cambridge, MA), relies on the modification of the Cas9 protein and guide RNA, so that there is only a nick in a single strand of the double helix.  The canonical Cas9 cuts both strands of DNA, and so relies on an efficient gap repair activity of the cell.  The second part, a new type of guide RNA called a pegRNA, contains an RNA template for a new DNA sequence to be added at the target location.  This pegRNA-directed synthesis of the new template requires the attachment of a reverse transcriptase enzymes to the Cas9.  So far Liu and his colleagues have tested the technology on over 175 human and rodent cell lines with great success.  In addition, they had also corrected mutations which cause Tay Sachs disease, which previous CRISPR systems could not do.  Liu claims that this technology could correct over 89% of pathogenic variants in human diseases.

A company Prime Medicine has been formed out of this effort.

Source: https://science.sciencemag.org/content/366/6464/406.abstract


Read an article on Dr. Liu, prime editing, and the companies that Dr. Liu has initiated including Editas Medicine, Beam Therapeutics, and Prime Medicine at https://www.statnews.com/2019/11/06/questions-david-liu-crispr-prime-editing-answers/

(interview by StatNews  SHARON BEGLEY @sxbegle)

As was announced, prime editing for human therapeutics will be jointly developed by both Prime Medicine and Beam Therapeutics, each focusing on different types of edits and distinct disease targets, which will help avoid redundancy and allow us to cover more disease territory overall. The companies will also share knowledge in prime editing as well as in accompanying technologies, such as delivery and manufacturing.

Reader of StatNews.: Can you please compare the pros and cons of prime editing versus base editing?

The first difference between base editing and prime editing is that base editing has been widely used for the past 3 1/2 years in organisms ranging from bacteria to plants to mice to primates. Addgene tells me that the DNA blueprints for base editors from our laboratory have been distributed more than 7,500 times to more than 1,000 researchers around the world, and more than 100 research papers from many different laboratories have been published using base editors to achieve desired gene edits for a wide variety of applications. While we are very excited about prime editing, it’s brand-new and there has only been one paper published thus far. So there’s much to do before we can know if prime editing will prove to be as general and robust as base editing has proven to be.

We directly compared prime editors and base editors in our study, and found that current base editors can offer higher editing efficiency and fewer indel byproducts than prime editors, while prime editors offer more targeting flexibility and greater editing precision. So when the desired edit is a transition point mutation (C to T, T to C, A to G, or G to A), and the target base is well-positioned for base editing (that is, a PAM sequence exists approximately 15 bases from the target site), then base editing can result in higher editing efficiencies and fewer byproducts. When the target base is not well-positioned for base editing, or when other “bystander” C or A bases are nearby that must not be edited, then prime editing offers major advantages since it does not require a precisely positioned PAM sequence and is a true “search-and-replace” editing capability, with no possibility of unwanted bystander editing at neighboring bases.

Of course, for classes of mutations other than the four types of point mutations that base editors can make, such as insertions, deletions, and the eight other kinds of point mutations, to our knowledge prime editing is currently the only approach that can make these mutations in human cells without requiring double-stranded DNA cuts or separate DNA templates.

Nucleases (such as the zinc-finger nucleases, TALE nucleases, and the original CRISPR-Cas9), base editors, and prime editors each have complementary strengths and weaknesses, just as scissors, pencils, and word processors each have unique and useful roles. All three classes of editing agents already have or will have roles in basic research and in applications such as human therapeutics and agriculture.

Nature Paper on Prime Editing CRISPR

Search-and-replace genome editing without double-strand breaks or donor DNA (6)


Andrew V. Anzalone,  Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa,

Luke W. Koblan, Jonathan M. Levy, Peter J. Chen, Christopher Wilson,

Gregory A. Newby, Aditya Raguram & David R. Liu


Nature volume 576, pages149–157(2019)



Most genetic variants that contribute to disease1 are challenging to correct efficiently and without excess byproducts2,3,4,5. Here we describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 endonuclease fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit. We performed more than 175 edits in human cells, including targeted insertions, deletions, and all 12 types of point mutation, without requiring double-strand breaks or donor DNA templates. We used prime editing in human cells to correct, efficiently and with few byproducts, the primary genetic causes of sickle cell disease (requiring a transversion in HBB) and Tay–Sachs disease (requiring a deletion in HEXA); to install a protective transversion in PRNP; and to insert various tags and epitopes precisely into target loci. Four human cell lines and primary post-mitotic mouse cortical neurons support prime editing with varying efficiencies. Prime editing shows higher or similar efficiency and fewer byproducts than homology-directed repair, has complementary strengths and weaknesses compared to base editing, and induces much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Prime editing substantially expands the scope and capabilities of genome editing, and in principle could correct up to 89% of known genetic variants associated with human diseases.



From Anzolone et al. Nature 2019 Figure 1.

Prime editing strategy

Cas9 targets DNA using a guide RNA containing a spacer sequence that hybridizes to the target DNA site. We envisioned the generation of guide RNAs that both specify the DNA target and contain new genetic information that replaces target DNA nucleotides. To transfer information from these engineered guide RNAs to target DNA, we proposed that genomic DNA, nicked at the target site to expose a 3′-hydroxyl group, could be used to prime the reverse transcription of an edit-encoding extension on the engineered guide RNA (the pegRNA) directly into the target site (Fig. 1b, cSupplementary Discussion).

These initial steps result in a branched intermediate with two redundant single-stranded DNA flaps: a 5′ flap that contains the unedited DNA sequence and a 3′ flap that contains the edited sequence copied from the pegRNA (Fig. 1c). Although hybridization of the perfectly complementary 5′ flap to the unedited strand is likely to be thermodynamically favoured, 5′ flaps are the preferred substrate for structure-specific endonucleases such as FEN122, which excises 5′ flaps generated during lagging-strand DNA synthesis and long-patch base excision repair. The redundant unedited DNA may also be removed by 5′ exonucleases such as EXO123.

  • The authors reasoned that preferential 5′ flap excision and 3′ flap ligation could drive the incorporation of the edited DNA strand, creating heteroduplex DNA containing one edited strand and one unedited strand (Fig. 1c).
  • DNA repair to resolve the heteroduplex by copying the information in the edited strand to the complementary strand would permanently install the edit (Fig. 1c).
  • They had hypothesized that nicking the non-edited DNA strand might bias DNA repair to preferentially replace the non-edited strand.


  • The authors evaluated the eukaryotic cell DNA repair outcomes of 3′ flaps produced by pegRNA-programmed reverse transcription in vitro, and performed in vitro prime editing on reporter plasmids, then transformed the reaction products into yeast cells (Extended Data Fig. 2).
  • Reporter plasmids encoding EGFP and mCherry separated by a linker containing an in-frame stop codon, +1 frameshift, or −1 frameshift were constructed and when plasmids were edited in vitro with Cas9 nickase, RT, and 3′-extended pegRNAs encoding a transversion that corrects the premature stop codon, 37% of yeast transformants expressed both GFP and mCherry (Fig. 1f, Extended Data Fig. 2).
  • They fused a variant of M—MLV-RT (reverse transcriptase) to Cas9 with an extended linker and this M-MLV RT fused to the C terminus of Cas9(H840A) nickase was designated as PE1. This strategy allowed the authors to generate a cell line containing all the required components of the primer editing system. They constructed 19 variants of PE1 containing a variety of RT mutations to evaluate their editing efficiency in human cells
  • Generated a pentamutant RT incorporated into PE1 (Cas9(H840A)–M-MLV RT(D200N/L603W/T330P/T306K/W313F)) is hereafter referred to as prime editor 2 (PE2).  These were more thermostable versions of RT with higher efficiency.
  • Optimized the guide (pegRNA) using a series of permutations and  recommend starting with about 10–16 nt and testing shorter and longer RT templates during pegRNA optimization.
  • In the previous attempts (PE1 and PE2 systems), mismatch repair resolves the heteroduplex to give either edited or non-edited products. So they next developed an optimal editing system (PE3) to produce optimal nickase activity and found nicks positioned 3′ of the edit about 40–90 bp from the pegRNA-induced nick generally increased editing efficiency (averaging 41%) without excess indel formation (6.8% average indels for the sgRNA with the highest editing efficiency) (Fig. 3b).
  • The cell line used to finalize and validate the system was predominantly HEK293T immortalized cell line
  • Together, their findings establish that PE3 systems improve editing efficiencies about threefold compared with PE2, albeit with a higher range of indels than PE2. When it is possible to nick the non-edited strand with an sgRNA that requires editing before nicking, the PE3b system offers PE3-like editing levels while greatly reducing indel formation.
  • Off Target Effects: Strikingly, PE3 or PE2 with the same 16 pegRNAs containing these four target spacers resulted in detectable off-target editing at only 3 out of 16 off-target sites, with only 1 of 16 showing an off-target editing efficiency of 1% or more (Extended Data Fig. 6h). Average off-target prime editing for pegRNAs targeting HEK3HEK4EMX1, and FANCFat the top four known Cas9 off-target sites for each protospacer was <0.1%, <2.2 ± 5.2%, <0.1%, and <0.13 ± 0.11%, respectively (Extended Data Fig. 6h).
  • The PE3 system was very efficient at editing the most common mutation that causes Tay-Sachs disease, a 4-bp insertion in HEXA(HEXA1278+TATC).


  1. Landrum, M. J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res44, D862–D868 (2016).
  2. Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science337, 816–821 (2012).
  3. Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science339, 819–823 (2013).


  1. Mali, P. et al. RNA-guided human genome engineering via Cas9. Science339, 823–826 (2013).
  2. Kosicki, M., Tomberg, K. & Bradley, A. Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements.  Biotechnol. 36, 765–771 (2018).
  3. Anzalone, A.V., Randolph, P.B., Davis, J.R. et al.Search-and-replace genome editing without double-strand breaks or donor DNA. Nature576, 149–157 (2019). https://doi.org/10.1038/s41586-019-1711-4

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