VIROLOGY MATTERS, Lecture notes of Virology

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UNIVERSITY OF CAPE TOWN DIVISION OF MEDICAL VIROLOGY BI-ANNUAL NEWSLETTER
VIROLOGY MATTERS
FEBRUARY 2019
Photo%credit:%Robyn%Walker%
1%
Prof. ANNA-LISE WILLIAMSON awarded SAMRC Gold Medal South%African% Medical%
Research% Council% Gold% medals% are% awarded% annually% to% established% senior% scien?sts% who% have% made%
seminal% scien?fic% contribu?ons% that% have% impacted% on% the% health% of% people,% especially% those% living% in%
developing% countries.% Anna-Lise% is% interna?onally% recognised% in% two% major% research% areas.% The% first% is%
vaccinology,% with% an% emphasis% on% the% development% of% novel% vaccines,% and% the% second% is% in% the% field% of%
human%papillomavirus%(HPV)%research.%
%
Anna-Lise% holds% a% South% African% Research% Chairs% Ini?a?ve% (SARChi)% research% chair% in% vaccinology% and% is%
ac?vely% training% many% postgraduate% students.% Her% standing% is% confirmed% by% an% H-index% of% 47% on% Google%
Scholar% and% her% work% has% been% cited% >6,500% ?mes.% We% congratulate% Anna-Lise% on% her% excep?onal%
achievements!%
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UNIVERSITY OF CAPE TOWN DIVISION OF MEDICAL VIROLOGY BI-ANNUAL NEWSLETTER

VIROLOGY MATTERS

FEBRUARY 2019

Photo credit: Robyn Walker

Prof. ANNA-LISE WILLIAMSON awarded SAMRC Gold Medal South African Medical

Research Council Gold medals are awarded annually to established senior scien?sts who have made

seminal scien?fic contribu?ons that have impacted on the health of people, especially those living in

developing countries. Anna-Lise is interna?onally recognised in two major research areas. The first is

vaccinology, with an emphasis on the development of novel vaccines, and the second is in the field of

human papillomavirus (HPV) research.

Anna-Lise holds a South African Research Chairs Ini?a?ve (SARChi) research chair in vaccinology and is

ac?vely training many postgraduate students. Her standing is confirmed by an H-index of 47 on Google

Scholar and her work has been cited >6,500 ?mes. We congratulate Anna-Lise on her excep?onal

achievements!

End Of Year Function

This year’s theme for the Virology End of Year

Func?on was “A Minute To Win It”, inspired by

the successful TV show. Contestants had 30

seconds to compete in a series of challenges. The

winners were the “What has Science Ever Done

for Us” Team from Prof Anna-Lise Williamson’s

research group.

Congratula?ons to the winning team!!!

New Staff and Students

DEAN KAYTON

I am a bioinforma?cian in the HIV Diversity Group, Division of

Medical Virology, University of Cape Town. I am a remote

working techie who enjoys living in fun and adventurous

loca?ons off the beaten track. I am currently residing in Kosi

Bay where I get to do things like watch baby turtles hatching,

go over to Mozambique for a daytrip, and sleep in caves in the

middle of nowhere. During the week I am connected up to

electricity and wifi, eyes glued to a laptop screen all day,

naviga?ng the internet for answers to problems which need

solving. I enjoy programming, data science and sta?s?cs. I am

fascinated by ar?ficial intelligence and machine learning,

something I am geing more and more involved in.

I enjoy that my career skills allow me to interface with

specialists in various different areas and I’m having a lot of fun

learning things I never knew about biology in my current role.

FAITH OGUNGBE

I am currently a student at Northwestern University in

Evanston, IL, USA geing my Master of Science degree in

Biotechnology. I graduated from Northwestern in 2017 with

my Bachelor of Arts degree in Anthropology, concentra?ng on

Human Biology with a minor in Business Ins?tu?ons. I am

currently comple?ng an internship with Dr Jo Ann Passmore’s

group to able to obtain my cer?ficate in Global Health and

Sustainability Biotechnologies for my degree. I have truly

enjoyed my experience in the lab and in Cape Town in general

and am excited to con?nue on with this wonderful learning

experience!

MICAELA LURIE

Micaela Lurie is a Masters student, specialising in Medical

Virology, con?nuing from an Honours degree in Immunology

and Infec?ous Diseases. Her work focuses on Chlamydia.

Outside of her academic career, she loves to travel and explore

new places. She func?ons on coffee and popcorn. A huge dog

lover who would one day love to adopt as many as possible.

Graduates

Dr Harris Onywera’s gradua?on,

surrounded by family and Prof

Anna-Lise Williamson

PhD

  • Smritee Dabee
  • Emmanuel

Margolin

  • Harris Onywera

Masters

  • Deelan Doolabh
  • Fatuma Guled
  • Valerie Masete

Honours

  • Bekiswa Abulele
  • Kate Bergh
  • Micaela Lurie
  • Temhlanga

Mndzebele

  • Keletso Phohlo

Daniel Sheward was awarded the 2018 Colin

Kaplan Award for his outstanding work in the field

of HIV pathogenesis. Daniel is the first author of a

manuscript published in the high impact journal,

Host Cell and Microbe (2017 impact factor:

17.872), en?tled “HIV Superinfec?on Drives De

Novo An?body Responses and not Neutraliza?on

Breadth”. The journal focuses broadly on the study

of microbes, with an emphasis on the interface

between the microbe and its host.

D a n i e l p l a y e d a n i n t e g r a l r o l e i n t h e

conceptualiza?on of the study including the

formula?on of the aims and methodology. He was

responsible for the data analysis, prepared all the

visualiza?ons and wrote the original drap(s) of the

manuscript.

The manuscript was well received by reviewers

(see excerpts below):

“This is a very important study that I believe will be

the seminal paper going forward on HIV

superinfec?on as it pertains to induc?on of bnAbs.

The study is technically sound and the study well

carried out.”

“The results obtained are important because they

debunk a 25 year old HIV-1 vaccine strategy to

generate broad and effec?ve an?-viral neutralizing

an?bodies that has repeatedly failed and should be

discarded: sequen?al immuniza?on with randomly

chosen heterologous Env immunogens present on

mature virus par?cles.”

“These are important findings building on

technically sound analyses.”

  • Prof Carolyn Williamson

Dean of the Faculty of Health Sciences

Colin Kaplan Award

DANIEL SHEWARD

At the end of 2018, A/Prof. Wendy Burgers took up her award of a Senior Fellowship from the European

and Developing Countries Clinical Trials Partnership (EDCTP). The project is en?tled CaTCH-22 -

C haracterizing the spectrum of T B and C o-infec?on with H IV - the role of Th 22 cells. It will run for the

next 5 years and is valued at over R8 million. The project seeks to understand the extraordinary

suscep?bility of HIV-infected individuals to developing TB, as well as demonstrate a role for different T

helper cell subsets in TB immune control, knowledge which can feed into the ra?onal design of a vaccine

for TB. In par?cular, the project hopes to characterise Th22 cells in TB immunity, and how these cells are

affected by HIV co-infec?on, HIV treatment and TB treatment.

Wendy says: “My team and I are very excited about this fellowship. Not only does it enable us to

con?nue our research in understanding immunity to TB during HIV co-infec?on, but also work on our

favourite cell subset, Th22 cells, which seem to be a limle unusual and HIV seems to like them a lot! Also,

it is essen?ally a capacity development grant – 2 PhD students, an MSc student and a postdoctoral fellow

will be trained over the course of the grant, while undertaking the research. A new postdoctoral fellow

and a Junior Research Fellow will join our team soon, and we look forward to discovering new things and

sharing our findings with the Division. Also to add - these are excellent grants to apply for, for anyone

doing clinical research, and there are fellowships available at senior and training levels. I have a very good

rela?onship with the EDCTP and regularly review EDCTP grants and fellowships, so have insight into what

they are looking for in their applica?ons. If anyone is interested in applying for these funding schemes, I

am happy to provide assistance and advice.”

A/Prof Wendy Burgers awarded EDCTP grant

HIV R4P Conference 2018

Thank you to Debbie Stewart for launching and compiling the

Virology Mamers newslemer for over 5 years!!

We had quite a con?ngent of the ALW plus group (I

am coun?ng in Gerald and Godfrey as well, they

are premy much honorary members) travelling to

R4P this year. Next to enjoying Madrid and the

great food there, we did some real science

ourselves but most importantly, some networking.

Here for instance we’re hanging with Gerald’s

buddies at the opening recep?on. Oh, one of them

turned out to be a journalist from Uganda who

covers scien?fic topics from Africa, so hopefully I

didn’t embarrass myself too much otherwise you’ll

be reading all about that soon.

Although no major breakthroughs were reported at

this HIVR4P mee?ng, the take-home message from

this conference by the leaders in the HIV-

preven?on field is that a vaccine with efficacy of

60% will be sufficient when combined with non-

vaccine based preven?on methods. This was

emphasized in three different plenary talks from

Linda-Gail Bekker, Anthony Fauci and John

Mascola. Although this sounded academically

convincing and a vaccine efficacy of 60% should be

achievable in the near future, I do wonder how this

would work in reality with (lack of) access and

adherence to non-vaccine based preven?on

methods. This first issue was further emphasized

by at least two other plenary talks in which

Maureen Luba gave the example that in her home

country of Malawi the only method of preven?on…

HIV R4P Conference 2018

Phindile presen?ng her Env

Zera-nanopar?cles.

Mani presen?ng his Env protein

produc?on plavorm in plants.

Opening recepLon

Dinner…

Dessert…

Coffee

Dinner… Most of us had

some nice Spanish food in

this busy restaurant, ranging

from lamb chops to pork ribs

which were washed down

with an excellent Rioja.

Godfrey, ordering a burger,

has clearly gone full-blown

American. No paella this ?me

around but we did gorge

o u r s e l v e s o n t h a t t h e

following day in a ?ny limle

place filled with locals.

Dessert… Aper leading us

wrongly to a bakery first,

Mani found us this great ice-

cream parlour in the centre

of town. The bakery did well

out of this limle detour with

M a n i ( s h a m e - ) b u y i n g

possibly one of the worst

c o o k i e s e v e r m a d e b y

mankind for a premy hepy

fee* as well.

  • N o t e v e n t a k i n g i n t o

account the exchange rate.

Coffee… Then we stumbled

on this cool limle coffee place

inside a hotel and I felt right

at home, look at this Delp

Blauw lobby!

RecepLon… Everyone hard at

work networking at the

opening recep?on. Judging by

her face, I think Gerald is

having a hard ?me convincing

the journalist next to him of

his point!

The Symposium was held from the 11

th to 15

th December at the Southern Cape Sun Hotel in Cape Town,

South Africa. One of the aims of the mee?ng was to bring HIV genital microbiome researchers together

with pregnancy and reproduc?ve health microbiome researchers to facilitate discussion and collabora?on

between the two groups whose research areas overlap substan?ally.

At the mee?ng the current understanding of female and male genital tract microbiology and immunology,

including func?onal microbiology and biofilms, was presented and knowledge gaps iden?fied. Poten?al

mechanisms leading to adverse outcomes, and a variety of poten?al preven?on and/or treatment

interven?ons, were presented and discussed. It was clear from the mee?ng that exponen?al progress has

been made in recent years and this will hopefully lead to efficacious public health interven?ons to reduce

the high prevalence of adverse sexual and reproduc?ve health outcomes in women, especially in

resource-poor seings.

A/Prof. Jo-Ann Passmore was Co-Chair of the mee?ng and many researchers from the Division of Virology

amended and presented their work, including Prof. Anna-Lise Williamson, Dr Lindi Masson, Dr Rubina

Bunjun, Lyle Curry, Dr Arghavan Alisoltanidehkordi, Anna Happel, Monalisa Manhanzva, Andrea

Abrahams, Dr Brian Kullin, and Dr Ramla Tanko among others.

Source: hmps://www.keystonesymposia.org/18S

Keystone Symposium

Genital Tract Microbiome in Sexual and Reproductive Health

The conference was held from the 2 nd to the 6 th October 2018 in Sydney, Australia. The aim of the mee?ng

was to provide a plavorm for sharing knowledge and research advances on human papillomavirus in

rela?on to cancer development, detec?on, epidemiology and preven?on. It covered a wide range of topics

including viral replica?on and life cycle, func?ons of oncoproteins, genome and RNA modifica?on and

regula?on, HPV tes?ng methodology and applica?on, pathogenesis, epidemiology, cancer screening and

public health issues. Areas related to cervical, anogenital, oropharyngeal and other cancers possibly

associated with HPV were also discussed. Some sessions also focused on HPV genomics with regards to

classifica?on, proposed new classifica?on and use of metagenomics and high throughput sequencing in

discovery of novel papillomavirus types.

The conference was amended by Prof. Anna-Lise Williamson, Dr Harris Onywera, Ongeziwe Taku and

Alltalents Murahwa.

- Alltalents Murahwa

32nd International Papillomavirus

Conference

Farewells

Bioinforma?cian, Dr Arghavan Alisoltanidehkordi had her

final day with the Masson group aper spending a year

working on cervicovaginal metaproteomics analysis. She has

moved to the University of California in the USA where she

is now working in the cancer and gene?cs field.

Her farewell party was hosted at the Mount Nelson on

January 31

st

  1. The group is sad to see her go but very

excited for her bright future.

Celia Rademeyer has been part of the

HIV Diversity Group for the last 9 years,

and she lep the group in 2018 to take a

break from science for a year or two.

Presently she is taking a more ac?ve

role in her and her husband’s business,

and she has also taken up teaching

pomery (a long-?me dream of hers).

Her full writeup can be seen in the Aug

2018 edi?on of the Newslemer. Her

formal going away was on the 19

th of

October 2018 at Deer Park Café.

Dr Ziyaad Valley-Omar

“I have been in or around the

Division of Medical Virology

since my honours year in 2002.

Back when the ethidium in our

gels was in black and white and

we made up our own mini prep

reagents (kids don’t know how

good they have it). It has been

an honour to study and work

under the guidance of

researchers that I hold in high

regard, who have facilitated

invaluable networking and research opportuni?es. At the

conclusion of my associa?on with the NICD in November, I

commenced with a medical scien?st posi?on within the Groote

Schuur NHLS ?ssue immunology diagnos?c laboratory where my

primary func?on is to setup high-resolu?on HLA typing

capabili?es by next genera?on sequencing for solid organ and

bone marrow transplant purposes. I am a molecular virologist at

heart (I think that’s a thing) and intend to con?nue virus-related

research efforts within my new posi?on through partnerships

with the Division of Virology. I have not lep and you will s?ll find

me lurking whenever and wherever there is cake.” 16

Marius Tincho

What’s the most interes?ng thing about you that we wouldn’t learn from your CV?

That I like to cook my own food thus I hardly eat out or order takeaways.

What is the funniest thing that has happened to you recently?

It may be the fact that many people assume that I am a Jehovah’s witness, because of the way I carry

myself or behave. Also because they assume that many people coming from Central African regional

countries are ChrisLans.

You’ve been given an elephant. You can’t give it away or sell it. What would you do with it?

An elephant is a very big animal and is an endangered species in many parts of the world. Taking it in

this perspecLve, I would return the animal to its natural habitat and make sure that it is taken care of.

On the other hand, it would be nice to lend the animal to others to transport their goods, or it can render

service to peoples. However, looking at the statement in a philosophical way, it would be a big

responsibility to receive such a massive giO and not be able to give it away or sell it. The elephant here

may symbolise, wealth, intellectual knowledge or any valuable item. Thus, it would be unreasonable not

to share it or give it to someone in need. The world we live today is at the crossroad of many turmoils

and we need to change our way of life and behaviour such that we can live together, share with one

another what we possess or have. It is only by given and sharing, help each other, come in need to

someone that we fulfil our true purpose earth, that we find happiness. Hence, I will celebrate the giO I

receive but sharing it with others and they would benefit from it even if they can possess it.

What would your autobiography be called?

“The journey of my life, the product of my efforts”

A penguin walks through that door right now wearing a sombrero.

What does he say and why is he here?

The penguin to me ”Is there a space for me in your house?”

Why is he here? “My habit has been destroyed and I need to adapt to the new situaLon”.

How would you describe your job to a child?

People are different and the way we act, behave, talk and even the way react to problem and happiness,

and it is the same when we become sick. For more than 30 years, there is a bad small animal, called HIV

that make many people become sick when it gets into their blood. Thanks to the fact that we are all

different, some people do not become sick and they can prevent the animal to destroy their body

because their body produces good soldiers that can help fight the bad animal. But other sick peoples

cannot produce these soldiers and they become very sick. And they can die if they are do not receive their

medicines. So, my work will consist of looking at the different substances which allow some sick peoples

to produce these good soldiers and some other sick peoples cannot produce them. I will also examine the

quanLLes of substances produced by sick peoples with good soldiers and compare them with the

quanLLes produced by sick peoples with weak or no soldiers. I will also examine how these quanLLes are

linked to the producLon of these good soldiers.

Getting to know the Virology

team with 6 quick questions

NaLonwide Danish study finds no

associaLon between measles,

mumps, rubella vaccinaLon and

auLsm

S i n c e t h e p u b l i c a? o n o f t h e

controversial Wakefield ar?cle in 1998

(that was subsequently retracted), the

possible link between measles, mumps,

rubella (MMR) vaccina?on and au?sm

has con?nued to cause concern, despite

10 subsequent observa?onal studies

finding no associa?on between MMR

and au?sm.

On Monday the 5

th of March 2019, a

na?onwide study published in Annals of

Internal Medicine (impact factor 19.4)

has found no increased risk of au?sm in

children who received MMR vaccina?on

in Denmark (adjusted hazard ra?o: 0.93;

95% confidence interval: 0.85 to 1.02).

This is one of the largest studies

conducted to date, including 657,

children born in Denmark over a ten-

year period. This study further validates

the results of another study, including

537,000 children that was conducted in

2002 and published in the New England

Journal of Medicine.

Despite this powerful evidence, it is

likely that vaccina?on hesitancy will

persist as parents con?nue to encounter

claims that vaccines cause au?sm on

social media and elsewhere.

Hviid, Anders et al. “Measles, Mumps, Rubella

Vaccina?on and Au?sm: A Na?onwide Cohort

Study.” Annals of Internal Medicine 2019. DOI:

10.7326/M18-

Hot off the press

(available at Annals.org). The crude effect sizes of sex, birth cohort, other early childhood vaccinations, sibling history of autism, and autism risk score are presented in Tables 2 and 3 of the Supplement (available at Annals.org). The high- est risk for autism was conferred by being a boy (HR, 4.02 [CI, 3.78 to 4.28]), being born in a late birth cohort (2008-2010; HR, 1.34 [CI, 1.18 to 1.52]), having no early childhood vaccinations (HR, 1.17 [CI, 0.98 to 1.38]), and having siblings with autism at study entry (HR, 7.32 [CI, 5.29 to 10.12]). The autism risk score had a modest

spectrum cases only resulted in aHRs of 0.96 (CI, 0. to 1.13) and 0.91 (CI, 0.82 to 1.02), respectively. In an analysis taking the second MMR dose into account, there was no evidence of a dose-response (increase in aHR per dose, 0.90 [CI, 0.85 to 0.95]). Adjustment for the potential confounders as covariates instead of strat- ification of the baseline hazard function did not affect the result (aHR, 0.93 [CI, 0.84 to 1.02]). Replacing the autism risk score with the individual covariates used to estimate it in the above model yielded an aHR of 0. (CI, 0.85 to 1.03).

Figure 2. Cumulative incidences of autism (unadjusted and with 95% CI bands) in 657 461 children born in Denmark between 1 January 1999 and 31 December 2010, by vaccination status and age.

Vaccinated Not vaccinated

0.

1 3 5 7 10 14

0.

1. Cumulative Incidence,

% 1.

2.

2.

Children at risk, n Vaccinated

Not vaccinated

3457

Age, y

654 004

571 550 493 444 391 259 235 016

66 497 36 343 27 392 18 949

37 267

823

Annals.org Annals of Internal Medicine 5

aded from https://annals.org by Univ of Cape Town Libraries user on 03/06/

DISCUSSION We found no support for the hypothesis of in- creased risk for autism after MMR vaccination in a na- tionwide unselected population of Danish children; no support for the hypothesis of MMR vaccination trigger- ing autism in susceptible subgroups characterized by environmental and familial risk factors; and no support

cal power and additional susceptible subgroup and clustering analyses. In a 2014 meta-analysis of MMR vac- cination and autism studies, 2 cohort and 4 case–control studies were identified from Denmark (5), Poland (17), Ja- pan (4, 18), the United Kingdom (19), and the United States (20), with no support for an association—for exam- ple, a pooled odds ratio from cohort studies of 0.84 (CI, 0.70 to 1.01) (2).

Figure 3. Association between measles, mumps, rubella vaccination and autism in subgroups of 657 461 children born in Denmark between 1 January 1999 and 31 December 2010.

Factor Hazard Ratio (95% CI)

Hazard Ratio (95% CI)

Cases, n Unvaccinated Vaccinated

P Value

All children Sex Male Female Birth cohort 1999– 2002– 2005– 2008– DTaP-IPV/Hib No DTaP-IPV/Hib 1 DTaP-IPV/Hib ≥2 DTaP-IPV/Hib Autism risk score group Very low risk Low risk Moderate risk High risk Sibling status at age 1 y No siblings with autism Siblings with autism No siblings Father’sID missing Time since vaccination First year Second year Third year Fourth year ≥4 years

0.93 (0.85–1.02)

0.97 (0.87–1.08) 0.79 (0.64–0.97)

0.84 (0.73–0.96) 1.04 (0.88–1.24) 1.02 (0.79–1.31) 0.94 (0.63–1.42)

1.09 (0.77–1.56) 0.92 (0.74–1.16) 0.92 (0.82–1.02)

0.93 (0.74–1.16) 0.86 (0.71–1.04) 0.91 (0.78–1.06) 1.06 (0.85–1.32)

0.98 (0.84–1.13) 2.69 (0.58–12.43) 0.89 (0.78–1.01) 0.89 (0.45–1.77)

0.96 (0.77–1.18) 0.88 (0.74–1.04) 0.91 (0.78–1.07) 0.96 (0.83–1.11) 0.94 (0.84–1.04)

525

416 109

260 158 75 32

64 92 369

91 133 206 95

227 5 283 10

NA NA NA NA NA

5992

4844 1148

2614 1937 1152 289

71 524 5397

1296 1637 2106 953

2297 32 3594 69

159 410 574 800 4049

0.

0.

>0.

>0.

>0.

>0.

0.50 0.75 0.93 1.5 2.

Fully adjusted autism hazard ratios comparing children who received measles, mumps, rubella vaccine with those who did not. The hazard ratios are depicted on a logarithmic scale, with bars representing 95% CIs. P values are from a test of homogeneity of effect. DTaP-IPV/Hib = diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type b vaccine; NA = not applicable.

ORIGINAL RESEARCH Measles, Mumps, Rubella Vaccination and Autism

High impact publications

Page 3

Have you heard?

Addressing vaccinaLon hesitancy through vaccine

communicaLon science

Studies to iden?fy the underlying reasons for vaccina?on failure are

cri?cal for designing vaccina?on interven?ons and campaigns to

increase uptake. A recent study used behaviour–disease interac?on

models to study how vaccine compliance can be influenced by a

wide range of factors.

1 Influen?al factors include lack of disease

awareness and misalignment between individual interest and the

popula?on interest. Another key factor is that vaccines are

imperfect in the sense that (i) there can exist unwanted, adverse

side effects of various degrees, albeit being minor most of the ?me,

and (ii) some vaccines only confer par?al protec?on against the

disease. These factors cause exaggerated perceived risk or cost of

vaccina?on compared to benefit.

In this study, the authors suggest that well-studied mechanisms for

promo?ng altruis?c behaviour can be used to improve vaccine

compliance.

1 Another study published in Nature reported that while

tradi?onal vaccina?on campaigns endorse harm and fairness,

individuals with high levels of vaccine hesitancy value liberty and

purity more highly than those with low hesitancy.

2 Inclusion of

these themes in vaccine discussions may improve coverage.

1 Chen, Xingru, and Feng Fu. "Imperfect vaccine and hysteresis." Proceedings of

the Royal Society B 286.1894 (2019): 20182406. 2 Amin, Avnika B., et al. "Associa?on of moral values with vaccine hesitancy."

Nature Human Behaviour 1.12 (2017): 873.

Precision CRISPR ediLng

The most popular gene-edi?ng tool, CRISPR-Cas9, generates breaks

in the genome that are subsequently repaired by a mix of cellular

pathways. Yet, the repair outcomes are not random. Using

machine-learning algorithms to analyze large amounts of Cas9-

mediated, genome-wide edi?ng events in a range of cells, Shen et

al. , Allen et al. , and Chakrabar? et al. uncovered sequence

determinants of repair outcomes and devised rules to predict

edi?ng products. These findings provide insights into the repair

process and instruct the design of guide RNAs to achieve more

precise edi?ng.

Mao, Steve. "Precision CRISPR edi?ng." Science 363.6424 (2019): 242-243.