PMID- 32924009
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2632-010X (Electronic)
IS  - 2632-010X (Linking)
VI  - 13
DP  - 2020 Jan-Dec
TI  - B-Cell-Targeted 3DNA Nanotherapy Against Indoleamine 2,3-Dioxygenase 2 (IDO2) 
      Ameliorates Autoimmune Arthritis in a Preclinical Model.
PG  - 2632010X20951812
LID - 10.1177/2632010X20951812 [doi]
LID - 2632010X20951812
AB  - The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase 2 (IDO2) has been 
      identified as an immunomodulatory agent promoting autoimmunity in preclinical 
      models. As such, finding ways to target the expression of IDO2 in B cells 
      promises a new avenue for therapy for debilitating autoimmune disorders such as 
      rheumatoid arthritis. IDO2, like many drivers of disease, is an intracellular 
      protein expressed in a range of cells, and thus therapeutic inhibition of IDO2 
      requires a mechanism for targeting this intracellular protein in specific cell 
      types. DNA nanostructures are a promising novel way of delivering small molecule 
      drugs, antibodies, or siRNAs to the cytoplasm of a cell. These soluble, branched 
      structures can carry cell-specific targeting moieties along with their 
      therapeutic deliverable. Here, we examined a 3DNA nanocarrier specifically 
      targeted to B cells with an anti-CD19 antibody. We find that this 3DNA is 
      successfully delivered to and internalized in B cells. To test whether these 
      nanostructures can deliver an efficacious therapeutic dose to alter autoimmune 
      responses, a modified anti-IDO2 siRNA was attached to B-cell-directed 3DNA 
      nanocarriers and tested in an established preclinical model of autoimmune 
      arthritis, KRN.g7. The anti-IDO2 3DNA formulation ameliorates arthritis in this 
      system, delaying the onset of joint swelling and reducing total arthritis 
      severity. As such, a 3DNA nanocarrier system shows promise for delivery of 
      targeted, specific, low-dose therapy for autoimmune disease.
CI  - (c) The Author(s) 2020.
FAU - Merlo, Lauren Mf
AU  - Merlo LM
AUID- ORCID: 0000-0002-5244-6448
AD  - Lankenau Institute for Medical Research, Wynnewood, PA, USA.
FAU - Bowers, Jessica
AU  - Bowers J
AD  - Genisphere, LLC, Hatfield, PA, USA.
FAU - Stefanoni, Tony
AU  - Stefanoni T
AD  - Genisphere, LLC, Hatfield, PA, USA.
FAU - Getts, Robert
AU  - Getts R
AD  - Genisphere, LLC, Hatfield, PA, USA.
FAU - Mandik-Nayak, Laura
AU  - Mandik-Nayak L
AUID- ORCID: 0000-0001-9030-3467
AD  - Lankenau Institute for Medical Research, Wynnewood, PA, USA.
LA  - eng
PT  - Journal Article
DEP - 20200827
PL  - United States
TA  - Clin Pathol
JT  - Clinical pathology (Thousand Oaks, Ventura County, Calif.)
JID - 101741182
PMC - PMC7457693
OTO - NOTNLM
OT  - 3DNA
OT  - IDO2
OT  - arthritis
OT  - autoimmunity
OT  - indoleamine 2,3-dioxygenase 2
COIS- Declaration of conflicting interests:The author(s) declared the following 
      potential conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: J.B. is Director of Academic Collaborations and 
      Marketing Communications, T.S. is a Research and Development Scientist, and R.G. 
      is Founder and Chief Scientific Officer of Genisphere LLC, the commercial 
      manufacturer of 3DNA. L.M.-N. and L.M.F.M. declare no conflict of interest.
EDAT- 2020/09/15 06:00
MHDA- 2020/09/15 06:01
PMCR- 2020/08/27
CRDT- 2020/09/14 05:57
PHST- 2020/07/16 00:00 [received]
PHST- 2020/07/30 00:00 [accepted]
PHST- 2020/09/14 05:57 [entrez]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2020/09/15 06:01 [medline]
PHST- 2020/08/27 00:00 [pmc-release]
AID - 10.1177_2632010X20951812 [pii]
AID - 10.1177/2632010X20951812 [doi]
PST - epublish
SO  - Clin Pathol. 2020 Aug 27;13:2632010X20951812. doi: 10.1177/2632010X20951812. 
      eCollection 2020 Jan-Dec.