View source for Locus Biosciences

{{Short description|Clinical phase American pharmaceutical company}}
{{Use mdy dates|date=April 2022}}
{{Infobox company
| name = Locus Biosciences
| logo = Locus_Biosciences_Logo.svg
| logo_size =
| logo_alt =
| logo_caption =
| logo_padding =
| image =
| image_size =
| image_alt =
| image_caption =
| trading_name =
| type = Privately held company
| traded_as =
| ISIN =
| industry = [[Pharmaceutical company]]
| founded = {{Start date and age|2015|05|22}} in [[Raleigh]], [[North Carolina|NC]], USA
| founders = {{unbulleted list
|Paul Garofolo<ref name="TC2"/><ref name=":0" />
|Nick Taylor
|Dave Ousterout
|Rodolphe Barrangou<ref name="PMID31021232">{{cite journal |url=https://pubmed.ncbi.nlm.nih.gov/31021232/ |title=CRISPR on the Move in 2019 |journal=The CRISPR Journal |date=2019 |pmid=31021232 |at=Affiliations |access-date=August 19, 2022 |last1=Barrangou |first1=R. |volume=2 |doi=10.1089/crispr.2019.29043.rba |s2cid=92382436 }}</ref>
|Charles Gersbach
|Chase Beisel
|Ahmed Gomaa
}}
| hq_location_city = [[Morrisville, North Carolina|Morrisville]], North Carolina
| hq_location_country = United States
| brands = crPhage
| production =
| production_year = <!-- Year of production data (if known) -->
| services =
| revenue =
| revenue_year = <!-- Year of revenue data (if known) -->
| operating_income =
| income_year = <!-- Year of operating_income data (if known) -->
| net_income = <!-- or: | profit = -->
| net_income_year = <!-- or: | profit_year = --><!-- Year of net_income/profit data (if known) -->
| assets =
| assets_year = <!-- Year of assets data (if known) -->
| equity =
| equity_year = <!-- Year of equity data (if known) -->
| owner = <!-- or: | owners = -->
| members =
| members_year = <!-- Year of members data (if known) -->
| num_employees = 80<ref name="Eanes2022"/>
| num_employees_year = 2021
| parent =
| divisions =
| subsid =
| website = {{URL|www.locus-bio.com/}}
| footnotes =
}}
'''Locus Biosciences''' is a clinical-stage [[pharmaceutical company]], founded in 2015 and based in [[Research Triangle Park]], [[North Carolina]].<ref name=":0">{{Cite news |last=Eanes |first=Zachery |date=March 9, 2021 |title=Locus using gene-editing technology to get ahead of drug-resistant bacteria |pages=B4 |work=[[The Herald-Sun (Durham, North Carolina)|The Herald-Sun]] |url=https://www.newspapers.com/clip/107926055/locus/ |access-date=August 19, 2022 |via=Newspapers.com}}</ref> Locus develops [[Phage therapy|phage therapies]] based on [[CRISPR#Cas genes and CRISPR subtypes|CRISPR–Cas3 gene editing]] technology, as opposed to the more commonly used [[CRISPR gene editing|CRISPR-Cas9]], delivered by engineered [[bacteriophage]]s.<ref name="Nature">{{cite journal |last1=Gibney |first1=Elizabeth |title=What to expect in 2018: science in the new year |journal=Nature |volume=553 |issue=7686 |pages=12–13 |date=January 2, 2018 |doi=10.1038/d41586-018-00009-5 |pmid=29300040 |bibcode=2018Natur.553...12G |doi-access=free }}</ref> The intended therapeutic targets are [[Antimicrobial resistance|antibiotic-resistant bacterial infections]].<ref name="TC2">{{cite news
|last=Buhr |first=Sarah
|url=https://techcrunch.com/2016/12/21/move-over-cas9-crispr-cas3-might-hold-the-key-to-solving-the-antibiotics-crisis/
|title=Move over Cas9, CRISPR-Cas3 might hold the key to solving the antibiotics crisis
|date=December 21, 2018
|work=TechCrunch
|access-date=July 18, 2020
|archive-url=https://web.archive.org/web/20190220100141/https://techcrunch.com/2016/12/21/move-over-cas9-crispr-cas3-might-hold-the-key-to-solving-the-antibiotics-crisis/
|archive-date=February 20, 2019
|url-status=live
}}</ref><ref name="Nature" />
== History ==
The company was founded as a [[University spin-off|spin-off]] from [[North Carolina State University]] (NCSU) in 2015 with licensed CRISPR patents from the university.<ref name="Gizmodo">{{cite news|last1=Brown|first1=Kristen V.|date=February 24, 2017|title=Scientists Are Creating a Genetic Chainsaw to Hack Superbug DNA to Bits|website=Gizmodo|publisher=G/O Media|url=https://gizmodo.com/a-little-known-crispr-technique-could-be-the-key-to-fig-1792689477|url-status=live|access-date=July 18, 2020|archive-url=https://web.archive.org/web/20181209122153/https://gizmodo.com/a-little-known-crispr-technique-could-be-the-key-to-fig-1792689477|archive-date=December 9, 2018}}</ref><ref name="TC">{{cite news |last=Shieber |first=Jonathan |date=January 4, 2019 |title=Up to $818&nbsp;million deal between J&J and Locus Biosciences points to a new path for CRISPR therapies |work=[[TechCrunch]] |url=https://techcrunch.com/2019/01/04/up-to-818-million-deal-between-jj-and-locus-biosciences-points-to-a-new-path-for-crispr-therapies/ |url-status=live |access-date=March 8, 2019 |archive-url=https://web.archive.org/web/20190203014835/https://techcrunch.com/2019/01/04/up-to-818-million-deal-between-jj-and-locus-biosciences-points-to-a-new-path-for-crispr-therapies/ |archive-date=February 3, 2019}}</ref> The company started with a $5&nbsp;million convertible note from [[Tencent Holdings]] and [[North Carolina Biotechnology Center]].<ref name="Biocentury1">{{cite news|last1=Martz|first1=Lauren|date=August 31, 2017|title=Cutting through resistance|work=Biocentury|url=https://www.biocentury.com/bc-innovations/product-rd/2017-08-31/how-locus-biosciences-using-crispr-cas3-tackle-antibiotic-?|url-access=limited<!--about 65% of article available without purchase-->|access-date=July 18, 2020}}</ref>
In 2017, the company closed a $19&nbsp;million [[Series A round|Series A]] led by Artis Ventures, [[Tencent]] Holdings Ltd, and Abstract Ventures.<ref name="TC" /><ref name="Biocentury1" /> In 2020, the company sold convertible notes in a debt raise to roll into its next equity round in 2021.<ref name="billion" />
In 2018, Locus acquired a high-throughput bacteriophage discovery platform from [[San Francisco Bay Area|San Francisco]]-based phage therapy company Epibiome, Inc.<ref name="epibiome">{{cite news |date=July 17, 2018 |title=Locus Biosciences Acquires EpiBiome Bacteriophage Discovery Platform |agency=Genomeweb |url=https://www.genomeweb.com/business-news/locus-biosciences-acquires-epibiome-bacteriophage-discovery-platform |url-access=registration |access-date=February 27, 2019}}</ref><ref>{{cite news|url=https://www.genengnews.com/news/crispr-cas3-platform-developer-locus-biosciences-acquires-epibiome-phage-technology/|date=July 17, 2018|title=CRISPR-Cas3 Platform Developer Locus Biosciences Acquires EpiBiome Phage Technology|work=Genetic Engineering & Biotechnology Nerws}}</ref>
In 2019, the company entered into a strategic collaboration with [[Janssen Pharmaceuticals]] (a [[Johnson & Johnson]] company) worth up to $818&nbsp;million to develop CRISPR-Cas3 drugs targeting two bacterial pathogens.<ref name="TC" /><ref name="JNJ">{{cite news |last1=Taylor |first1=Phil |title=J&J takes stake in Locus' CRISPR-based 'Pac-Man' antimicrobials |url=https://www.fiercebiotech.com/biotech/j-j-takes-stake-locus-crispr-based-pac-man-antimicrobials |access-date=February 27, 2019 |agency=Fierce Biotech |date=January 3, 2019 |archive-url=https://web.archive.org/web/20190306192547/https://www.fiercebiotech.com/biotech/j-j-takes-stake-locus-crispr-based-pac-man-antimicrobials |archive-date=March 6, 2019 |url-status=live  }}</ref><ref name="wired">{{cite magazine |last=Molteni |first=Megan |date=January 16, 2019 |title=Antibiotics Are Failing Us. Crispr is Our Glimmer of Hope |url=https://www.wired.com/story/antibiotics-are-failing-us-crispr-is-our-glimmer-of-hope/ |url-status=live |magazine=Wired |archive-url=https://web.archive.org/web/20190123205808/https://www.wired.com/story/antibiotics-are-failing-us-crispr-is-our-glimmer-of-hope/ |archive-date=January 23, 2019 |access-date=March 8, 2019}}</ref><ref name="sciam">{{cite journal |last=Schmidt |first=Charles |date=November 1, 2019 |title=Is Phage Therapy Here to Stay? |url=https://www.scientificamerican.com/article/phage-therapy-could-beat-drug-resistant-illnesses/ |journal=[[Scientific American]] |pages=50–57 |access-date=October 23, 2019}}</ref> Locus received $20&nbsp;million upfront and up to $798&nbsp;million in milestones and royalties on net sales.<ref name="Bloomberg">{{cite news |last1=Brown |first1=Kristen |date=January 3, 2019 |title=J&J Bets $20 Million on DNA Tool to Battle Infectious Bacteria |agency=Bloomberg |url=https://www.bloomberg.com/news/articles/2019-01-03/j-j-bets-20-million-on-dna-tool-to-battle-infectious-bacteria |url-access=subscription |access-date=February 27, 2019}}</ref>
In 2020, the company signed a $12.5&nbsp;million partnership with the global non-profit, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).<ref name="billion" /> In November 2020, Locus had 52 employees;<ref name="billion">{{Cite news |last=Maurer |first=Allan |date=November 19, 2020 |title=Gene editing success could turn Triangle startup Locus Biosciences into a billion dollar unicorn |work=WRAL TechWire |publisher=[[Capitol Broadcasting Company]] |url=https://www.wraltechwire.com/2020/11/19/gene-editing-success-could-turn-triangle-startup-locus-biosciences-into-a-billion-dollar-unicorn/}}</ref> by the end of 2021, it had about 80 employees.<ref name="Eanes2022">{{Cite news |last=Eanes |first=Zachery |date=January 29, 2022 |title=Locus Biosciences is eyeing immunology for its CRISPR tech |volume=158 |pages=A6 |work=[[The News & Observer]] |issue=29 |url=https://www.newspapers.com/clip/107931372/locus-biosciences/ |access-date=August 19, 2022 |via=Newspapers.com}}</ref> As of January 2022, the company and all employees were contained in a single 25,000 square foot research and manufacturing facility.<ref name="Eanes2022" />
In 2022, the company closed a $35&nbsp;million [[Series B]] funding round, with participation from Artis Ventures, Tencent, [[Viking Global Investors]], and Johnson & Johnson.<ref>{{cite news|url=https://www.biopharma-reporter.com/Article/2022/05/19/bacteriophage-producer-locus-biosciences-raises-35m-in-financing|author=Jane Byrne|date=May 19, 2022|title=Bacteriophage producer Locus Biosciences raises $35m in financing|work=BioPharma Reporter}}</ref> Locus announced in September 2022 that it had begun patient treatment in its trial of LBP-EC01, in partnership with the [[Biomedical Advanced Research and Development Authority|BARDA]], for the treatment of [[urinary tract infection|UTIs]] caused by [[Escherichia coli|E coli bacteria]].<ref>{{cite news|url=https://www.pmlive.com/pharma_news/locus_biosciences_announces_first_patient_treated_in_urinary_tract_infection_trial_1455586|author=Emily Kimber|date=September 15, 2022|title=Locus Biosciences announces first patient treated in urinary tract infection trial|work=PM Live}}</ref>
[[File:Phage injecting its genome into bacteria.svg|thumb|Phage injecting its genome into bacterial cell]]
== CRISPR CAS3 ==
{{main|CRISPR}}
CRISPR-Cas3 is more destructive than the better known CRISPR–Cas9 used by companies like Caribou Biosciences, [[Editas Medicine]], Synthego, [[Intellia Therapeutics]], [[CRISPR Therapeutics]] and Beam Therapeutics.<ref name="TC" /> CRISPR–Cas3 destroys the targeted [[DNA]] in either [[prokaryotic]] or [[eukaryotic]] cells.<ref name="JNJ" /><ref name="Nature2">{{cite journal |doi=10.1038/nature.2017.22173|pmid=28661508|title=Modified viruses deliver death to antibiotic-resistant bacteria|journal=Nature|volume=546|issue=7660|pages=586–587|year=2017|last1=Reardon|first1=Sara|bibcode=2017Natur.546..586R|doi-access=free}}</ref> Co-founder, Rodolphe Barrangou, said "Cas3 is a meaner system...but if you want to cut a tree and get rid of it, you bring a chain saw, not a scalpel".<ref name="wsj">{{cite news |last1=Marcus |first1=Amy Dockser |title=A Genetic 'Chain Saw' to Target Harmful DNA |agency=Wall Street Journal |url=https://www.wsj.com/articles/a-genetic-chain-saw-to-target-harmful-dna-1477081818 |url-status=live |url-access=limited |access-date=February 27, 2019 |archive-url=https://web.archive.org/web/20180306074907/https://www.wsj.com/articles/a-genetic-chain-saw-to-target-harmful-dna-1477081818 |archive-date=March 6, 2018}}</ref>
CRISPR-Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is divided into types II, V, and VI.<ref name="Wright2016">{{cite journal | vauthors = Wright AV, Nuñez JK, Doudna JA | title = Biology and Applications of CRISPR Systems: Harnessing Nature's Toolbox for Genome Engineering | journal = Cell | volume = 164 | issue = 1–2 | pages = 29–44 | date = January 2016 | pmid = 26771484 | doi = 10.1016/j.cell.2015.12.035 | doi-access = free }}</ref> The 6 system types are divided into 19 subtypes.<ref name="Westra2016">{{cite journal | last1 = Westra | first1 = Edze R. | last2 = Dowling | first2 = Andrea J. | last3 = Broniewski | first3 = Jenny M. | last4 = van Houte | first4 = Stineke | name-list-style = vanc | title = Evolution and Ecology of CRISPR | journal = Annual Review of Ecology, Evolution, and Systematics | date = November 2016 | volume = 47 | issue = 1 |pages = 307–331 | doi = 10.1146/annurev-ecolsys-121415-032428 | url = https://zenodo.org/record/3452297 | doi-access = free }}</ref> Many organisms contain multiple CRISPR-Cas systems suggesting that they are compatible and may share components.<ref name="pmid22337052">{{cite journal | vauthors = Wiedenheft B, Sternberg SH, Doudna JA | title = RNA-guided genetic silencing systems in bacteria and archaea | journal = Nature | volume = 482 | issue = 7385 | pages = 331–8 | date = February 2012 | pmid = 22337052 | doi = 10.1038/nature10886 | bibcode = 2012Natur.482..331W | s2cid = 205227944 }}</ref><ref name="pmid23320564">{{cite journal | vauthors = Deng L, Garrett RA, Shah SA, Peng X, She Q | title = A novel interference mechanism by a type IIIB CRISPR-Cmr module in Sulfolobus | journal = Molecular Microbiology | volume = 87 | issue = 5 | pages = 1088–99 | date = March 2013 | pmid = 23320564 | doi = 10.1111/mmi.12152 | doi-access = free }}</ref>
{| class="wikitable"
|+ Difference between CRISPR-Cas3 and CRISPR-Cas9
|-
! Class !! Cas type !! Signature protein !! Function !! Reference
|-
| 1 || I || Cas3 || Single-stranded DNA nuclease (HD domain) and ATP-dependent helicase ||<ref name="pmid21343909">{{cite journal | vauthors = Sinkunas T, Gasiunas G, Fremaux C, Barrangou R, Horvath P, Siksnys V | title = Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system | journal = The EMBO Journal | volume = 30 | issue = 7 | pages = 1335–42 | date = April 2011 | pmid = 21343909 | pmc = 3094125 | doi = 10.1038/emboj.2011.41 }}</ref><ref name="ReferenceB">{{cite journal | vauthors = Huo Y, Nam KH, Ding F, Lee H, Wu L, Xiao Y, Farchione MD, Zhou S, Rajashankar K, Kurinov I, Zhang R, Ke A | title = Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation | journal = Nature Structural & Molecular Biology | volume = 21 | issue = 9 | pages = 771–7 | date = September 2014 | pmid = 25132177 | pmc = 4156918 | doi = 10.1038/nsmb.2875 }}</ref>
|-
| 2 || II || [[Cas9]] || [[Nuclease]]s RuvC and HNH together produce [[double-strand breaks|DSBs]], and separately can produce single-strand breaks. Ensures the acquisition of functional spacers during adaptation. ||<ref name="pmid22949671">{{cite journal | vauthors = Gasiunas G, Barrangou R, Horvath P, Siksnys V | title = Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 39 | pages = E2579–86 | date = September 2012 | pmid = 22949671 | pmc = 3465414 | doi = 10.1073/pnas.1208507109 | bibcode = 2012PNAS..109E2579G | doi-access = free }}</ref><ref>{{cite journal | vauthors = Heler R, Samai P, Modell JW, Weiner C, Goldberg GW, Bikard D, Marraffini LA | title =  Cas9 specifies functional viral targets during CRISPR–Cas adaptation| journal = Nature | volume = 519 | issue = 7542 | pages = 199–202 | date = March 2015 | pmid = 25707807 | pmc = 4385744 | doi = 10.1038/nature14245 | bibcode = 2015Natur.519..199H }}</ref>
|-
|}
==Therapy development==
The company enrolled its first patient in a [[Phase 1 clinical trial|Phase 1b clinical trial]] in January 2020. The trial intends to evaluate LBP-EC01, a CRISPR Cas3-enhanced bacteriophage against ''Escherichia coli'' bacteria which cause [[urinary tract infections]].<ref name="start">{{cite web |title=Locus Biosciences initiates world's first controlled clinical trial for a CRISPR enhanced bacteriophage therapy |date=January 8, 2020 |url=https://www.locus-bio.com/media/locus-biosciences-initiates-worlds-first-controlled-clinical-trial/ |access-date=January 11, 2020}}</ref> Twenty patients will get a phage cocktail, and 10 will get a placebo.<ref name="MorningNPR">{{cite news |title=Scientists Modify Viruses With CRISPR To Create New Weapon Against Superbugs |url=https://www.npr.org/sections/health-shots/2019/05/22/723582726/scientists-modify-viruses-with-crispr-to-create-new-weapon-against-superbugs |access-date=May 28, 2019 |agency=NPR |date=May 22, 2019}}</ref> The trial completed before March 2021 and a [[Phase II trial]] is expected to start within two years.<ref name=":0" /> The company has an agreement the US government's [[Biomedical Advanced Research and Development Authority]] which began in 2020 and provides funding to support Phase II and [[Phase III trials]].<ref name=":0" /><ref name="billion" />
== Publications ==
As of 2022, there are no peer-reviewed publications that are solely or primarily authored by Locus Biosciences staff.<ref>{{Cite web |title=Locus Biosciences[Affiliation] - Search Results - PubMed |url=https://pubmed.ncbi.nlm.nih.gov/?term=Locus+Biosciences%5BAffiliation%5D&sort= |access-date=2022-08-20 |website=PubMed |language=en}}</ref>
==References==
{{reflist}}
[[Category:Pharmaceutical companies of the United States]]
[[Category:Gene therapy]]
[[Category:Health care companies based in North Carolina]]
[[Category:Bacteriophages]]
[[Category:2015 establishments in North Carolina]]
[[Category:University spin-offs]]