CRISPR is one of the latest big things in DNA research, but don't expect designer babies or an attack of the clones anytime soon.
What makes this therapy unique is that it uses a gene-editing technology known as CRISPR, which allows for precise and efficient editing of the genetic code.
But this doesn't mean human gene modification is about to go viral.
Rather, this is a safe and sensible technology that has the power to help the 300,000 babies born with sickle cell disease each year and the nearly 10 million people estimated to suffer from this genetic disorder globally.
That's if patients can access the treatment and if ways are found to cover the high up-front costs of more than USD$2 million per patient.
However, don't expect designer babies or an attack of the clones anytime soon.
Sickle cell disease is caused by a single letter misspelling — think of it like a critical typo — in the gene encoding adult globin, a component of hemoglobin, a molecule found in red blood cells that is important for carrying oxygen to the muscles and tissues throughout your body.
This genetic mutation or misspelling affects the configuration of the adult globin molecules, causing them to stick together and form long chains that can change the shape of red blood cells — making them look like sickles.
The cells block narrow blood vessels and damage tissues — virtually every tissue. Patients suffer from pain and eventual organ failure.
While the symptoms of sickle cell disease can be managed in part through various medications, via blood transfusions, and in some cases by bone marrow transplants from matched siblings, limitations in the feasibility and efficacy of these treatments meant that scientists have continued to search for a proper cure.
First generation CRISPR technologies — and this is the first — allow us to cut the double helix DNA molecule in whatever location, in any gene or in regions between genes, that we choose.
Then natural DNA repair processes in the cell stitch the ends together, usually making a small deletion, just as tying a knot in a piece of string might.
First generation techniques cannot efficiently correct spelling mistakes, they just make deletions and in effect rub out words.
While this technique couldn't correct the genetic typo causing sickle cell disease, it addressed the root cause of the disease in another way.
Researchers — and I'm one of them — who had been investigating the biology of globin genes for decades had noted that some people with the sickle cell disease mutation were virtually free of symptoms, because another gene saved them.
They were expressing a 'super' globin, fetal globin that binds oxygen tightly and allows babies to draw oxygen from their mother's blood when in utero.
Usually this gene is turned off at birth but a few people keep it on. It can stand in for the mutant adult globin gene.
Remarkably, these people are just fine.
They are walking around, living normal lives. They just have a second mutation that stops the 'super globin' fetal globin gene from being turned off.
The new therapy mimics the mutations in these people. It involves cutting and destroying one key DNA sequence to keep fetal globin on. So fetal globin does its job and the symptoms of sickle cell disease go away.
If that sounds complicated, that's because it is.
Instead of correcting the mutation, researchers have knocked out the off-switch of a different gene to turn that gene on, and that super globin is curing the disease. It's a double negative.
Researchers took this convoluted route for two reasons.
First, sickle cell disease is just one of a hundred or more highly related disorders caused by different mutations that affect the production or function of adult globin.
This approach represents a universal cure — researchers don't have to design CRISPR strategies to correct all the different mutations.
Second, while, as you may have heard, CRISPR can correct mutations efficiently in the lab, it turns out that making corrections with first generation CRISPR is not very efficient in blood stem cells.
Next generation gene editing
Newer gene-editing approaches are also being developed.
For example, base editing enables some misspellings of the four DNA bases — the chemical building blocks of DNA, adenine, cytosine, guanine and thymine, commonly represented as A, C, G and T respectively — to be corrected but the chemistry of DNA is such that one cannot yet change every letter into every other letter.
Another technique, called prime editing, should be like 'find and replace' in a word processing program, but we don't know if it is efficient enough for gene therapy yet.
Even if it is, that doesn't mean people will start building brand new people or superhuman soldiers.
The human genome is like a city. Think of the sickle cell disease mutation as a pothole that blocks a road. At present we are fixing the road block by just knocking down a gate, so traffic can get round via an alternative track — the fetal globin route.
Even if base editing and prime editing work, all we'll be doing is repairing a road here and there.
This therapy involves taking blood stem cells from patients, modifying them, and putting them back.
It's complicated, that's why it is an expensive treatment. But families are not changed genetically, there are no mothers carrying mutant embryos. It is 'opt in' for the patient. It will occur one patient at a time and cannot 'go viral'.
Perhaps one day we will have to sit down to discuss human modification, but for now we are fixing potholes that affect the blood of some people.
A small thing for humanity perhaps, but a huge change for those with this lifelong genetic disease.
Professor Merlin Crossley is Deputy Vice-Chancellor Academic Quality and a professor of molecular biology at UNSW. His lab works on CRISPR gene editing to treat inherited blood diseases.
Professor Crossley's research on sickle cell disease and gene editing were funded by grants from the Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC). Professor Crossley also receives funding via an Australian Research Council Linkage Grant with CSL Behring.
CRISPR ni moja ya mambo makubwa ya hivi karibuni katika utafiti wa DNA, lakini usitarajie watoto wa kubuni au shambulio la clones wakati wowote hivi karibuni. Tiba hii ni ya kipekee kwa sababu inatumia teknolojia ya kuhariri jeni inayojulikana kama CRISPR, ambayo inaruhusu uhariri sahihi na ufanisi wa nambari ya maumbile. Lakini hii haimaanishi kwamba mabadiliko ya jeni ya binadamu yanakaribia kuwa ya virusi. "Hii ni teknolojia salama na yenye busara ambayo ina nguvu ya kusaidia watoto 300,000 wanaozaliwa na ugonjwa wa seli ya sickle kila mwaka na watu karibu milioni 10 wanaokadiriwa kuteseka na ugonjwa huu wa urithi ulimwenguni kote. """ "Hiyo ni ikiwa wagonjwa wanaweza kupata matibabu na ikiwa njia zinapatikana za kulipia gharama za juu za mbele za zaidi ya dola milioni 2 kwa kila mgonjwa. """ Hata hivyo, usitarajie watoto waliobuniwa au shambulio la kloni hivi karibuni. Ugonjwa wa seli ya msalaba unatokana na herufi moja iliyoandikwa vibaya - fikiria kama makosa muhimu ya kuandika - katika jeni inayotangaza globin ya watu wazima, sehemu ya hemoglobini, molekuli inayopatikana katika seli nyekundu za damu ambayo ni muhimu kwa kubeba oksijeni kwa misuli na tishu katika mwili wako. Mabadiliko haya ya maumbile huathiri muundo wa molekuli za globini za watu wazima, na kusababisha viungo vyao viunganishwe na kuunda minyororo mirefu ambayo inaweza kubadilisha umbo la chembe nyekundu za damu - na kuifanya ionekane kama nyundo. Chembe hizo hufungi mishipa nyembamba ya damu na kuharibu tishu - karibu tishu zote. Wagonjwa hupatwa na maumivu na hatimaye kushindwa kwa viungo. Ingawa dalili za ugonjwa wa seli za mviringo zinaweza kudhibitiwa kwa sehemu kupitia dawa mbalimbali, kupitia uingizaji damu, na katika baadhi ya kesi kwa upandikizaji wa uti wa mgongo kutoka kwa ndugu na dada waliofanana, mapungufu katika uwezekano na ufanisi wa matibabu haya yalimaanisha kwamba wanasayansi wameendelea kutafuta tiba sahihi. Teknolojia ya CRISPR ya kizazi cha kwanza, ambayo ni ya kwanza, inatuwezesha kukata molekuli ya DNA ya helisi mbili katika eneo lolote, katika jeni lolote au katika mikoa kati ya jeni, ambayo tunachagua. Kisha, kwa njia ya utaratibu wa asili wa kurekebisha DNA, sehemu hizo mbili za nyuzi huunganishwa pamoja, na kwa kawaida kutoweka kidogo, kama vile kufunga kamba katika kamba ya kamba. Mbinu za kizazi cha kwanza haziwezi kusahihisha makosa ya herufi kwa ufanisi, zinafanya tu kufuta na kwa kweli kufuta maneno. Ingawa mbinu hiyo haikuweza kurekebisha kosa la kuchapa la chembe za urithi lililosababisha ugonjwa wa seli za mviringo, ilitatua kisababishi kikuu cha ugonjwa huo kwa njia nyingine. Watafiti - na mimi ni mmoja wao - ambao walikuwa wakichunguza biolojia ya jeni la globin kwa miongo kadhaa walikuwa wameona kwamba watu fulani wenye mabadiliko ya ugonjwa wa seli ya sickle walikuwa karibu bila dalili, kwa sababu jeni nyingine iliwaokoa. "Globini ya ""super"" ya fetal, ambayo huunganisha oksijeni kwa nguvu na kuruhusu watoto kupata oksijeni kutoka kwa damu ya mama yao wakati wa mimba." Kwa kawaida jeni hilo hufutwa wakati wa kuzaliwa lakini watu wachache huendelea kulitumia. Inaweza kuchukua nafasi ya jeni la globini ya mtu mzima lililobadilika. Kwa kushangaza, watu hawa ni wazuri sana. Wao hutembea-tembea, wakiishi maisha ya kawaida. Wana mabadiliko ya pili tu ambayo huzuia jeni la'super globin' la globin ya kijusi lisizunguliwe. Tiba hiyo mpya huiga mabadiliko ya chembe za urithi katika watu hao. Upasuaji huu unahusisha kukata na kuharibu mfululizo mmoja muhimu wa DNA ili kuweka globini ya kiinitete. Kwa hiyo globini ya kiinitete hufanya kazi yake na dalili za ugonjwa wa chembe za mviringo hupungua. Ikiwa hilo linaonekana kuwa gumu, ni kwa sababu ni gumu. Badala ya kurekebisha mabadiliko hayo, watafiti wamegonga kiunganishi cha jeni tofauti ili kuamsha jeni hilo, na superglobin hiyo inaponya ugonjwa huo. Ni kinyume mara mbili. Watafiti walichukua njia hiyo yenye kutatanisha kwa sababu mbili. Ugonjwa wa seli ya msalaba ni moja tu ya magonjwa zaidi ya mia moja yanayohusiana na ugonjwa wa seli ya msalaba, yanayosababishwa na mabadiliko tofauti ya chembe za urithi ambayo huathiri uzalishaji au kazi ya globin ya watu wazima. Njia hii inawakilisha tiba ya ulimwengu wote <unk> watafiti hawana kubuni mikakati ya CRISPR kurekebisha mabadiliko yote tofauti. Kwa mfano, CRISPR inaweza kurekebisha mabadiliko ya chembe za msingi za damu kwa ufanisi katika maabara, lakini kwa chembe za msingi za damu, CRISPR haifanyi kazi vizuri. Uhariri wa jeni wa kizazi kijacho Njia mpya za uhariri wa jeni pia zinatengenezwa. Kwa mfano, kuhariri msingi huwezesha baadhi ya makosa ya herufi ya misingi minne ya DNA - vipande vya kemikali vya DNA, adenine, cytosine, guanine na thymine, kwa kawaida huwakilishwa kama A, C, G na T - kurekebishwa, lakini kemia ya DNA ni kama mtu bado hawezi kubadilisha kila herufi katika herufi nyingine zote. "Utaratibu mwingine unaoitwa ""prime editing"" unafanana na ""tafuta na ubadilishe"" katika programu ya usindikaji wa maneno, lakini hatujui ikiwa ni ufanisi wa kutosha kwa matibabu ya jeni." Hata kama ni hivyo, hiyo haimaanishi watu wataanza kujenga watu wapya kabisa au askari wa hali ya juu. Genome ya binadamu ni kama mji. Fikiria ugonjwa wa chembe za mviringo kama shimo linaloziba barabara. Kwa sasa tunatengeneza kizuizi cha barabara kwa kubomoa lango tu, ili trafiki iweze kuzunguka kupitia njia mbadala <unk> njia ya globini ya kiinitete. Hata kama uhariri wa msingi na uhariri wa msingi unafanya kazi, tutafanya ni kurekebisha barabara hapa na huko. Tiba hiyo inahusisha kuchukua chembe za msingi za damu kutoka kwa wagonjwa, kuzibadilisha, na kuzirudisha. Ni ngumu, ndiyo sababu ni matibabu ya gharama kubwa. Lakini familia hazibadiliki kwa maumbile, hakuna akina mama wanaobeba viini-tete vilivyobadilika. Ni 'kujiunga' kwa ajili ya mgonjwa. Itatokea mgonjwa mmoja kwa wakati na haiwezi 'kuenda virusi'. """Labda siku moja tutakuwa na kuketi chini kujadili mabadiliko ya binadamu, lakini kwa sasa tunatengeneza mashimo ambayo huathiri damu ya watu wengine." Ni jambo dogo kwa wanadamu, lakini ni mabadiliko makubwa kwa wale walio na ugonjwa huu wa urithi wa maisha yote. Profesa Merlin Crossley ni Naibu Makamu wa Kansela wa Ubora wa Chuo na profesa wa biolojia ya molekuli katika UNSW. Maabara yake inafanya kazi ya kuhariri jeni ya CRISPR kutibu magonjwa ya damu yanayopatikana kwa urithi. Utafiti wa Profesa Crossley juu ya ugonjwa wa seli ya sickle na uhariri wa jeni ulifadhiliwa na ruzuku kutoka kwa Baraza la Utafiti la Australia (ARC) na Baraza la Kitaifa la Afya na Utafiti wa Matibabu (NHMRC). Crossley pia hupokea ufadhili kupitia Australia Utafiti Baraza Linkage Grant na CSL Behring.