SCIENTIFIC READING AND WRITING ASSIGNMENT
YOUR NAME ________________________________________________________________
COURSE_____________________________________________________________________
Exercise 1.1: Find a primary scientific research article
Title: _________________________________________________________________________
______________________________________________________________________________
Citation: The scientific research paper is located:
Journal name __________________________________________________________________
Year _________________________________________________________________________
Issue # (if applicable) ___________________________________________________________
Volume # (if applicable) _________________________________________________________
Page # s_______________________________________________________________________
Exercise 1.2: Citation
1. Identify the first author(s) (it is authors if there is a reference to "equal contributing authors")
The first author (s)___________________________________________________________
___________________________________________________________________________
2. Identify affiliation (2h3r3 they work) for the first author (s)
3.
XXXXXXXXXXThe first author (s) affiliation _________________________________________________________
XXXXXXXXXX________________________________________________________________________
Provide the full properly formatted CSE citation:
Exercise 1.3: Abstract
1. Is the abstract organized in the traditional way with four major parts?
Yes_____ No_____
2. Does the abstract depart from tradition? If so, describe how it is different. If not, what are the four major parts? In your own words provide one descriptive sentence which is specific to your article for each part of the abstract.
Exercise 1.4: Introduction
1. Why did the author (s) conduct the research?
2. What was the hypothesis, prediction, or objective of this study?
3. Was there enough background information given for a scientist in the field to identify and understand the question (s) or problem (s) that will be addressed by the research? Yes______ No____________
Explain your answer thoroughly (What did the authors describe that you needed to know to understand the questions- what was not described by the authors?)
Exercise 1.4: Results and Conclusions
1. Write a paragraph describing the researcher’s key results. Be specific- give numbers and facts. Don’t simply say “the found a bigger of this than this”. How much bigger (ie 25% increase etc)- was it significant?
2. Choose one of the experimental methods used to support a key finding of the paper. Do some research on the method. Describe how the method is used in general. Briefly describe how it is performed.. What can it be used to tell the investigator? How was in used in this paper to test the hypothesis?
Exercise 1.5: Discussion
1. What where the researchers main conclusions? Which findings were used to support specific conclusion(s) and why do such findings support this conclusion (rather than some other conclusion) Specifically link three results with the conclusion they support.
2.Do the results and conclusions support or differ from the original hypothesis? Explain your answer.
3. What does the author suggest is the major contribution of this study (why is it important to the field/society)?
XXXXXXXXXXWhat questions remain for further research?
Exercise 1-6: Related literature
Find two other papers closely related to the topic of the one you chose. Provide the co
ect complete citation for each paper.
Describe the search strategy you used to find these papers (Include databases and key words used)
Describe how the findings of this paper relate to those in your paper. Did their result confirm, contrast, or extend the findings in your original paper? How?
6
Cell Biology: Dr. Ca
oll Sum 21
The Journal of Clinical Investigation R E S E A R C H A R T I C L E
8 2 7jci.org Volume 130 Number 2 Fe
uary 2020
Introduction
In just over four decades since its global emergence, the AIDS epi-
demic has taken millions of lives. While there have been exceptional
advances in antiretroviral therapies, there remains a need for pre-
ventive treatments and interventions to eliminate HIV-1 infection
(1). In recent years, multiple mAbs with potent neutralization capac-
ity have been isolated from HIV-1–infected persons (2, 3). A few of
these
oadly neutralizing HIV-1 mAbs (bNAbs) have demonstrated
efficacy in preventing infection after a single dose of intravenous
ecombinant protein in nonhuman primates (NHPs) (4). Such obser-
vations have generated enthusiasm in the field and progressed HIV-
1 bNAbs into the clinic for studies of prevention (ClinicalTrials.gov
NCT XXXXXXXXXX, NCT XXXXXXXXXX, NCT XXXXXXXXXXas well as for HIV
treatment toward cure strategies (5–9). Recently, clinical trials have
explored the capability of these antibodies to lower viral loads or
prevent rebound after analytical treatment inte
uption (ATI) (8, 9).
Most notably, a study by Mendoza et al. demonstrated that a combi-
nation of 2 bNAbs, 3BNC117 and XXXXXXXXXX, prevented viral rebound
for a median of 21 weeks in a subset of individuals compared with 2.3
weeks in historical controls (6).
The widespread use of passive delivery of recombinant
antibodies is affected due to infusion time, formulation issues,
product temperature stability, redosing requirements, and sub-
stantial manufacturing costs (10). Viral vector delivery with adeno-
associated virus (AAV) has been previously evaluated as a delivery
platform for HIV-1 bNAbs, with high-level and long-term expres-
sion of the transgene antibody (11–13). However, AAV delivery can
e limited in populations by preexisting neutralizing antibodies
to the vector, safety concerns of permanent gene marking of the
patient, temperature stability, and manufacturing cost as well as
vector seroconversion potentially preventing readministration,
ultimately resulting in reduced antibody levels in many subjects
(14). Recent clinical results of recombinant AAV-1–delivered PG9
demonstrated limited detection of circulating PG9 in healthy
males who were delivered a range of vector doses (4 × 1012 to 1.2
× 1014 vector genomes XXXXXXXXXXIn this study, we explored the use
of synthetic DNA-encoded mAbs (dmAbs) as a possible alterna-
tive, serology-independent approach to passive transfer and AAV
delivery. Upon injection and electroporation of optimized plasmid
DNA with transgenes encoding antibody, locally transfected cells
ecome the in vivo biofactory for antibody production. We have
previously demonstrated that this dmAb technology was able to
Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous
oadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for
potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries,
long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their
potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for
direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied
their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with
activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased
neutralization
eadth. Two dmAbs, PGDM1400 and PGT121, were advanced into nonhuman primates for study. High peak-
circulating levels (between 6 and 34 μg/ml) of these dmAbs were measured, and the sera of all animals displayed
oad
neutralizing activity. The dmAb approach provides an important local delivery platform for the in vivo generation of HIV-1
NAbs and for other infectious disease antibodies.
In vivo delivery of synthetic DNA–encoded antibodies
induces
oad HIV-1–neutralizing activity
Megan C. Wise,1 Ziyang Xu,2,3 Edgar Tello-Ruiz,2 Charles Beck,4 Aspen Trautz,2 Ami Patel,2 Sarah T.C. Elliott,2 Neethu Chokkalingam,2
Sophie Kim,2 Melissa G. Kerkau,4 Kar Muthumani,2 Jingjing Jiang,1 Paul D. Fisher,1 Stephany J. Ramos,1 Trevor R.F. Smith,1
Janess Mendoza,1 Kate E. Broderick,1 David C. Montefiori,5 Guido Fe
ari,4 Daniel W. Kulp,2 Laurent M. Humeau,1 and David B. Weiner2
1Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA. 2Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA. 3Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania, USA. 4Duke Human Vaccine Institute and 5Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
Authorship note: MCW and ZX contributed equally to this work.
Conflict of interest: MCW, JJ, PF, SJR, TRFS, JM, KEB, and LH are employees of Inovio
Pharmaceuticals and, as such, receive salary and benefits, including ownership of
stock and stock options. KM receives grants and consulting fees from Inovio Phar-
maceuticals related to DNA vaccine development. DBW has received grant funding,
participates in industry collaborations, has received speaking honoraria, and has
eceived fees for consulting, including serving on scientific review committees and
oard series. Remuneration received by DBW includes direct payments, stock, or
stock options, and, in the interest of disclosure, he notes potential conflicts associ-
ated with his work with Inovio Pharmaceuticals and possibly others. MCW and DBW
have a pending US patent, XXXXXXXXXX.
Copyright: © 2020, American Society for Clinical Investigation.
Submitted: August 19, 2019; Accepted: October 24, 2019; Published: January 6, 2020.
Reference information: J Clin Invest. 2020;130(2):827–837.
https:
doi.org/10.1172/JCI132779.
https:
www.jci.org
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www.jci.org/130/2
https:
doi.org/10.1172/JCI132779
The Journal of Clinical Investigation R E S E A R C H A R T I C L E
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uary 2020
Figure 1. In vivo expression of dmAb-encoded HIV-1 bNAbs in mice. (A) Peak dmAb expression levels (d14) of bNAbs in the sera of transiently
immunodepleted mice. Groups of mice (n = 5) were administered dmAb constructs expressing 1 of 16 different bNAbs. (B) Binding curves for 4 dmAbs
against HIV-1 trimer BG505_MD39. Serum dmAb levels were normalized for expression (colored lines, n = 5 mice) and compared with the similar
purified recombinant protein (black lines) over various concentrations. (C) Individual mouse IC50 (n = 5) for 4 dmAbs across the 12 viruses of the global
panels (blue circles) versus values reported in the literature (red squares). Literature values gathered from Los Alamos CATNAP. (D) Mean (n = 5) IC50
pseudotype neutralization of d14 mouse sera against the 12 viruses of the global panel and MLV control. Value of 45 co
esponds to no neutralization
at a 1:45 dilution, the lowest dilution of the mouse serum tested. All other values are in μg/ml. Horizontal bars indicate mean; e
or bars represent
SEM. Expression levels are representative of 2 experimental replicates; binding and neutralization testing were performed once.
https:
www.jci.org
https:
www.jci.org
https:
www.jci.org/130/2
The Journal of Clinical Investigation R E S E A R C H A R T I C L E
8 2 9jci.org Volume 130 Number 2 Fe
uary 2020
Next, we proceeded to assess in vivo expression in transient-